Effectiveness of Combined Hemodialysis-Hemadsorption Therapy in Improving Uremic Toxin Clearance, Inflammatory Markers, and Symptoms in Maintenance Hemodialysis Patients.

INTRODUCTION: Combined hemodialysis (HD) and hemadsorption (HA) therapy has shown the highest clearance rates for middle and large-sized uremic toxin molecules and reduced mortality rates among maintenance HD (MHD) patients. This study aims to investigate the effectiveness of combined HD and HA therapy in patients undergoing MHD. METHODS: Forty patients with end-stage renal disease (ESRD) were divided into three groups: HD only (14), HD+biweekly HA (14), and HD+weekly HA (12). The duration of the study was 8 weeks. Uremic toxins (ß2-microglobulin, leptin, parathyroid hormone), inflammatory markers (interleukin-6, C-reactive protein), and symptoms (appetite, pruritus, sleep quality) were assessed before the start and at the completion of therapy. Changes in the parameters were compared between the three groups. Mean differences of parameters in each group were also compared between before and after therapy. RESULTS: Decrease in BUN level (-61.34 mg/dL [95% CI:-71.33 to -51.34], p <0.0001) and pruritus score (-3.93 [95% CI:-6.89 to -0.97], p=0.013) was significantly larger in HD+biweekly HA group compared to the others. Only HD + biweekly HA group showed significant reductions in CRP level (-0.10 mg/L [95%: -0.18 to -0.01], p=0.034), VAS appetite score (10.43 [95% CI: 4.99 to 15.87], p = 0.001), and pruritus score (-3.93 [95% CI: -6.89 to -0.97], p =0.013) after therapy. Both HD+biweekly HA (-2.79 [95% CI: -4.97 to -0.60], p=0.016) and HD+weekly HA group (-2.33 [95% CI: -4.59 to -0.08], p=0.044) exhibited a significant improvement in sleep quality score after therapy. CONCLUSIONS: HD combined with a biweekly HA is associated with a greater reduction in BUN level and better improvement of pruritus in ESRD patients compared to HD alone. HD+biweekly HA can significantly reduce CRP levels, alleviate pruritus, improve appetite, and enhance sleep quality.

Association of Acute Hyperglycemia and Diabetes Mellitus with Platelet-derived Microparticle (PDMP) Levels During Acute Myocardial Infarction.

Objectives: This research investigates whether there is an association between acute hyperglycemia and diabetes mellitus and the level of circulating platelet-derived microparticles (PDMPs) during an initial episode of acute myocardial infarction (AMI). Methodology: This was a cross-sectional study involving hospitalized AMI patients. Demographic and clinical data were obtained from hospital records. Diabetes mellitus was defined by the history of the disease, anti-diabetes medication use and/ or level of HbA1C ≥6.5%. Levels of HbA1c, admission random and fasting blood glucose levels were measured. Flow-cytometry method was used to determine the levels of PDMPs from collected venous blood through tagging with CD-41 FITC and CD-62 PE markers and a threshold size of <1 µm. The number of circulating PDMPs was compared according to glucometabolic state, namely acute hyperglycemia (admission random glucose ≥200 mg/dL and fasting glucose ≥140 mg/dL) and diabetes mellitus. The comparative analysis between groups was conducted with Student T-test or Mann-Whitney test, where applicable. Results: A total of 108 subjects were included and their data analyzed. The level of circulating PDMPs was significantly lower in subjects with admission random glucose ≥200 mg/dL as compared to those with below level [median (interquartile range (IQR)]: 2,710.0 (718.0-8,167.0) count/mL vs. 4,452.0 (2,128.5-14,499.8) count/mL, p = 0.05) and in subjects with fasting glucose ≥140 mg/dL as compared to those with below level (median (IQR): 2,382.0 (779.0-6,619.0) count/mL vs. 5,972.0 (2,345.7-14,781.3) count/mL, p = 0.006). The level of circulating PDMPs was also significantly lower in patients with diabetes mellitus as compared to those without (median (IQR): 2,655.0 (840.0-5,821.0) count/mL vs. 4,562.0 (2,128.5-15,055.8) count/mL; p = 0.007). Conclusion: Acute hyperglycemia and diabetes mellitus are significantly associated with a lower circulating PDMP level during an initial AMI episode.

Increased endothelin-1 levels in coronary artery disease with diabetes mellitus in an Indonesian population.

Diabetes mellitus (DM) increases risk of coronary artery disease (CAD). Endothelin-1 (ET-1) is a potential biomarker of endothelial dysfunction. This study aimed to evaluate ET-1 level in CAD patients and its relationship with DM. The cross-sectional design included subjects with angiographically proven CAD and controls among Indonesian. DM was defined by medical history and anti-diabetics use. Serum ET-1 level was measured in both subject groups. We recruited 305 subjects, 183 CAD patients and 122 controls. CAD subjects had higher percentage of males, DM, hypertension, dyslipidemia, smoking, family history of cardiovascular disease, and obesity. ET-1 level was significantly higher in CAD than in controls (2.44 ± 1.49 pg/mL vs. 1.76 ± 0.83 pg/mL; p < 0.001). Increased ET-1 level was significantly associated with DM and dyslipidemia. The highest ET-1 level was observed in CAD with DM, followed by CAD non-DM (2.79 ± 1.63 pg/mL vs. 2.29 ± 1.40 pg/mL; p = 0.023). Among controls, ET-1 level was the lowest in non-DM subjects. Female CAD had higher proportion of DM; however, ET-1 level was similar to male CAD with DM. In conclusion, an increased ET-1 level was significantly associated with DM in patients with CAD. Further research should investigate the potential role of ET-1 receptor antagonists in the secondary prevention of CAD with DM.

High Level of Mid-Regional Proadrenomedullin during ST-Segment Elevation Myocardial Infarction Is an Independent Predictor of Adverse Cardiac Events within 90-Day Follow-Up.

Background and Objectives: the cardiovascular adverse events including mortality and heart failure, persist significantly during the first months after the acute phase of ST-segment elevation myocardial infarction (STEMI). The increased level of midregional proadrenomedullin (MR-proADM), at hospital presentation in STEMI patients is considered an independent predictor of short-term and long-term mortality and heart failure. This study aimed to measure MR-proADM levels during the acute and recovery phases of STEMI and corroborate whether MR-proADM level was associated with the adverse cardiac events after recovering from STEMI. Materials and Methods: this prospective study enrolled subjects with acute phase STEMI admitted to the intensive cardiac care unit. After recovering and discharged from hospitalization, subjects were followed-up for 90 days. For MR-proADM measurement, the blood samples during acute phase were withdrawn on hospital admission (MR-proADM-0) and during recovery at the day-30 follow up (MR-proADM-30). Adverse cardiac events were evaluated at 30-day and 90-day follow up, namely a composite of death, chronic heart failure, and hospital readmission of any cardiac causes. Results: 83 subjects were enrolled. The median MR-proADM-0 was 3313.33 pg/mL and MR-proADM-30 was significantly reduced at 292.50 pg/mL, p < 0.001. Nineteen subjects (22.9%) experienced adverse cardiac events at 30-day follow up. The MR-proADM-0 level was independently associated with 30-day adverse cardiac events (adjustedOR 1.002, 95%CI: 1.001−1.003, p = 0.040), after adjustment with other variables. In this case, 25 subjects (32.5%) experienced adverse cardiac events at 90-day follow-up. The MR-proADM-0 level was independently associated with 90-day adverse cardiac events (adjustedOR 1.002, 95%CI: 1.001−1.003, p = 0.049). The higher changes of MR-proADM-0 to MR-proADM-30 also associated with adverse cardiac events at 90 days. Conclusions: The MR-proADM was significantly increased during the acute phase of STEMI and declined during recovery phase. The higher MR-proADM level during the acute phase of STEMI and its change intensity were predictors of adverse cardiac events within the 90-day follow up.

Evaluation of Human Leukocyte Antigen Class I and Class II in End-Stage Renal Disease Occurrence in Indonesian Transplantation Patients.

BACKGROUND: Genetic studies of end-stage renal disease (ESRD), including those of human leukocyte antigen (HLA) genes, have been reported in several populations but have not yet been evaluated in Indonesia. Some studies have reported that these genes had a substantial role in ESRD. This study aims to analyze the association between HLA genes and ESRD within the Indonesian community. METHOD: A retrospective study to investigate HLA class I and II alleles to find out the distribution of HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1 in renal transplant recipients and to ascertain their role in susceptibility to ESRD was performed on totally 149 subjects, consisting of 69 ESRD patients and 80 healthy controls. HLA typing was determined using Luminex techniques. The allele and haplotype frequencies were compared between ESRD patients and controls. RESULT: High-frequency alleles were HLA-A∗24 (43.6%), B∗15 (38.2%), C∗08 (30.8%), DRB1∗12 (47.3%), DQB1∗03 (50.6%), and DPB1∗13 (22.5%). HLA-A∗24 (p=0.01) and HLA-B∗35 (p=0.02) were associated with a protective effect, with OR 0.537 (95%CI 0.34-0.86) and 0.316 (95%CI 0.11-0.88), respectively. There were some two-locus haplotypes associated with susceptibility to ESRD, such as B∗15-DRB1∗12, B∗13-DRB1∗15, A∗02-B∗15, A∗02-C∗08, and B∗13-DQB1∗05. HLA-A∗02-B∗15-DRB1∗12 and A∗24-B∗13-DRB1∗15 appear to be associated with susceptibility to ESRD. CONCLUSION: The allele groups of HLA-A∗24 and HLA-B∗35 are associated with protection from ESRD. Meanwhile, HLA-B∗13-DRB1∗15 and A∗24-B∗13-DRB1∗15 are the most frequent HLAs associated with ESRD in two-locus and three-locus haplotype, respectively.

Serum endothelin-1 level positively correlates with waist and hip circumferences in stable coronary artery disease patients.

Central obesity is associated with increased level and activity of endothelin-1. The waist and hip circumferences are simple indicators of central obesity. Waist circumference correlates with visceral adiposity, whereas hip circumference associates with gluteofemoral peripheral adiposity. Both measurements have independent and opposite correlation with coronary artery disease (CAD) risk factors. The relation between serum endothelin-1 in stable CAD and both parameters of central obesityneeds to be investigated. This study aims to examine the correlation between serum endothelin-1 level and waist and hip circumferences as parameters of central obesity in patients with stable CAD. This was a cross-sectional study. Consecutive subjects were enrolled among those who underwent elective coronary angiography with significant CAD. Serum endothelin-1 was measured from peripheral blood samples taken before coronary angiography procedure. The measurement of waist circumference, hip circumference, and ratio derived from them, was performed. Central obesity was determined by waist circumference cut-off for Indonesian population. The correlation analysis was performed with Pearson test. The multivariate analysis was performed with multiple linear regression test. The comparison of serum endothelin-1 level between groups was performed with Student T test. We enrolled 50 subjects. The majority of subjects was male (80.0%), hypertensive (86.0%), dyslipidemic (68%) and smoker (52%). Most subjects had history of acute coronary syndrome (64%). Mean waist circumference was 87.6 +/- SD cm, hip circumference was 95.3 cm +/- SD, mean waist-to-hip ratio was 0.92 +/- SD and mean waist-to-height ratio was 0.54 +/- SD. Central obesity occurred in 32% of subjects. Mean serum endothelin-1 level was 2.2 ± 0.7 pg/mL. Serum endothelin-1 level tended to be higher in subjects with central obesity as compared to those without. Serum endothelin-1 level was significantly correlated with age, hemoglobin level, waist circumference (coefficient of 0.311, p value = 0.023) and hip circumference (coefficient of 0.359, p value = 0.010). Multivariable analysis indicated that age (coefficient of -0.353, p value = 0.007) and hip circumference (coefficient of 0.335, p value = 0.011) were independently correlated with serum endothelin-1. For conclusion, in patients with stable CAD, serum endothelin-1 was positively correlated with both waist circumference and hip circumference. Hip circumference independently and positively correlated with serum endothelin-1 level.

Molecular epidemiology of SARS-CoV-2 isolated from COVID-19 family clusters.

BACKGROUND: Transmission within families and multiple spike protein mutations have been associated with the rapid transmission of SARS-CoV-2. We aimed to: (1) describe full genome characterization of SARS-CoV-2 and correlate the sequences with epidemiological data within family clusters, and (2) conduct phylogenetic analysis of all samples from Yogyakarta and Central Java, Indonesia and other countries. METHODS: The study involved 17 patients with COVID-19, including two family clusters. We determined the full-genome sequences of SARS-CoV-2 using the Illumina MiSeq next-generation sequencer. Phylogenetic analysis was performed using a dataset of 142 full-genomes of SARS-CoV-2 from different regions. RESULTS: Ninety-four SNPs were detected throughout the open reading frame (ORF) of SARS-CoV-2 samples with 58% (54/94) of the nucleic acid changes resulting in amino acid mutations. About 94% (16/17) of the virus samples showed D614G on spike protein and 56% of these (9/16) showed other various amino acid mutations on this protein, including L5F, V83L, V213A, W258R, Q677H, and N811I. The virus samples from family cluster-1 (n = 3) belong to the same clade GH, in which two were collected from deceased patients, and the other from the survived patient. All samples from this family cluster revealed a combination of spike protein mutations of D614G and V213A. Virus samples from family cluster-2 (n = 3) also belonged to the clade GH and showed other spike protein mutations of L5F alongside the D614G mutation. CONCLUSIONS: Our study is the first comprehensive report associating the full-genome sequences of SARS-CoV-2 with the epidemiological data within family clusters. Phylogenetic analysis revealed that the three viruses from family cluster-1 formed a monophyletic group, whereas viruses from family cluster-2 formed a polyphyletic group indicating there is the possibility of different sources of infection. This study highlights how the same spike protein mutations among members of the same family might show different disease outcomes.

Serum Endothelin-1 Correlates with Myocardial Injury and Independently Predicts Adverse Cardiac Events in Non-ST-Elevation Acute Myocardial Infarction.

INTRODUCTION: Serum endothelin-1 is increasingly released in acute myocardial infarction, by necrotic cardiomyocytes. In non-ST-elevation acute myocardial infarction (Non-STEMI), increased serum endothelin-1 on-admission may have clinical significance during acute hospitalisation events. OBJECTIVE: The purpose of this study is to investigate whether increased serum endothelin-1 level predict adverse cardiac events in patients hospitalized with Non-STEMI. METHODS: The design of this research was a prospective cohort study. Consecutive subjects with Non-STEMI undergoing symptom onset ≤24 hour were enrolled and observed during intensive hospitalization. Serum endothelin-1, troponin-I, and hs-C reactive protein were measured from peripheral blood taken on-admission. In-hospital adverse cardiac events were a composite of death, acute heart failure, cardiogenic shock, reinfarction, and resuscitated VT/VF. RESULTS: We enrolled 66 subjects. The incidence of in-hospital adverse cardiac events is 13.6% (10 out of 66 subjects). Serum endothelin-1 level was significantly higher in subjects with in-hospital adverse cardiac events. Subjects with endothelin-1 level >2.59 pg/mL independently predicted adverse cardiac events in hospitalised Non-STEMI patients (adjusted odds ratio 44.43, 95% confidence interval: 1.44-1372.99, p value 0.03). The serum endothelin-1 level was correlated with serum troponin I level (correlation coefficient of 0.413, p value 0.012). CONCLUSION: Increased serum endothelin-1 on-admission correlated with increased troponin-I and independently predicted in-hospital adverse cardiac events in patients with Non-STEMI.

Circulating Platelet-Derived Microparticles Associated with Postdischarge Major Adverse Cardiac Events in ST-Elevation Acute Myocardial Infarction.

INTRODUCTION: Platelet-derived microparticles (PDMPs) measurement adds prognostic implication for ST-elevation acute myocardial infarction (STEMI). The long-term implication of PDMPs in STEMI needs to be corroborated. METHODS: The research design was a cohort study. Subjects were STEMI patients and were enrolled consecutively. The PDMPs were defined as microparticles bearing CD41(+) and CD62P(+) markers detected with flow cytometry. The PDMPs were measured on hospital admission and 30 days after discharge. The outcomes were major adverse cardiac events (MACE), i.e., a composite of cardiac death, heart failure, cardiogenic shock, reinfarction, and resuscitated ventricular arrhythmia, occurring from hospitalization until 1 year after discharge. RESULTS: We enrolled 101 subjects with STEMI. During hospitalization, 17 subjects (16.8%) developed MACE. The PDMPs were not different between subjects with MACE and those without (median (IQR): 3305.0/µL (2370.0-14690.5/µL) vs. 4452.0/µL (2024.3-14396.8/µL), p=0.874). Forty-five subjects had increased PDMPs in 30 days after discharge as compared with on-admission measurement. Subjects with increased PDMPs had significantly higher 30-day MACE as compared to subjects with decreased PDMPs 17 (37.8%) vs. 6 (16.7%, p=0.036). There was a trend toward higher MACE in subjects with increased PDMPs as compared to those with decreased PDMPs in 90 days after discharge (48.9% vs. 30.6%, p=0.095) and 1 year after discharge (48.9% vs. 36.1%, p=0.249). CONCLUSION: The PDMPs level was increased from the day of admission to 30 days after discharge in patients with STEMI. The persistent increase in the PDMPs level in 30 days after the STEMI event was associated with the 30-day postdischarge MACE and trended toward increased MACE during the 90-day and 1-year follow-up.

The ratio of circulating endothelin-1 to endothelin-3 associated with TIMI risk and dynamic TIMI risk score in ST elevation acute myocardial infarction.

In ST segment elevation acute myocardial infarction (STEMI), the endothelin (ET) system imbalance, reflected by the circulating ET-1:ET-3 ratio has not been investigated. This study's primary objective was to measure the circulating ET-1:ET-3 ratio and correlate it with the risk stratification for 1 year mortality of STEMI based on TIMI score. On admission, the TIMI risk score and at discharge, the dynamic TIMI risk score were calculated in 68 consecutive subjects with STEMI. Subjects with high TIMI risk score were associated with higher mean ET-1 level and ET-1:ET-3 ratio. The ET-1:ET-3 ratio more accurately predicted the high on admission TIMI risk score than the ET-1 level. Subjects with high dynamic TIMI risk score were associated with higher mean ET-1 level and ET-1:ET-3 ratio. The ET-1:ET-3 ratio more accurately predicted the high at discharge dynamic TIMI risk score than ET-1 level. From multivariable analysis, the ET-1:ET-3 ratio was not independently associated with high on admission TIMI risk score but independently predicted high at discharge dynamic TIMI risk score (odds ratio = 9.186, p = 0.018). In conclusion, combining the ET-1 and ET-3 levels into the ET-1:ET-3 ratio provided a prognostic value by independently predicting the increased risk to 1 year mortality as indicated by at discharge dynamic TIMI risk score in patients with STEMI.

The Utility of Point of Care Test for Soluble ST2 in Predicting Adverse Cardiac Events during Acute Care of ST-Segment Elevation Myocardial Infarction.

INTRODUCTION: Soluble ST2 (sST2) is increased during acute myocardial infarction. The point of care test (POCT) for sST2 is currently available. The aim of this study was to investigate the utility of the sST2 POCT measurement for predicting adverse cardiac events during acute care of ST-elevation myocardial infarction (STEMI). PATIENTS AND METHODS: This research used a cohort study design. Consecutive patients with STEMI were enrolled. Soluble ST2 level was measured from peripheral blood taken on admission with POCT. Observation during acute intensive care was conducted to record adverse cardiac events. Two groups were assigned based on median sST2 level, that is, supramedian and inframedian group. The incidence of adverse cardiac events between groups was analyzed. A p value < 0.05 was statistically significant. RESULTS: We analyzed 95 subjects with STEMI and 10 patients with stable coronary artery disease as controls. The median sST2 level was significantly higher in subjects with STEMI as compared to controls (152.1 ng/mL versus 28.5 ng/mL, p < 0.01). Among subjects with STEMI, the supramedian group had higher incidence of adverse cardiac events than the inframedian group (38.3% versus 12.5%, p=0.004). Multivariable analysis showed that supramedian sST2 level was independently associated with increased incidence of adverse cardiac events (adjusted OR 6.27; 95% CI: 1.33-29.47, p=0.020). CONCLUSIONS: The sST2 POCT measurement was useful to independently predict adverse cardiac events during acute intensive care of STEMI.

Platelet microparticle number is associated with the extent of myocardial damage in acute myocardial infarction.

INTRODUCTION: Activated platelets generate microparticles. Increased platelet microparticles occur in acute myocardial infarction (AMI) and contribute to intracoronary thrombosis and subsequent myocardial injury. This study aimed to investigate the impact of platelet microparticles on intracoronary thrombosis by assessing the relationship between platelet microparticles and the extent of myocardial damage in AMI. MATERIAL AND METHODS: This was a cross sectional study. The subjects were patients with acute coronary syndrome (ACS). Forty-one consecutive subjects with ACS admitted to intensive cardiovascular care unit were enrolled. The clinical spectrum of ACS comprised AMI (n = 26), both ST-elevation AMI (STEMI) and non-ST-elevation AMI (NSTEMI), and unstable angina (n = 15). Platelet microparticles were isolated from peripheral venous blood and detected with anti-CD42b-PE by the flow cytometry method. The extent of myocardial damage was determined by measuring the peak level of serial cardiac enzymes within 24 h of admission. RESULTS: Subjects with AMI had a significantly higher number of platelet microparticles than those with unstable angina (4855 ±4509/µl vs. 2181 ±1923/µl respectively; p = 0.036). Subjects with STEMI had the highest number of platelet microparticles, but no significant difference was detected as compared to those with NSTEMI (5775 ±5680/µl vs. 3601 ±1632/µl). The number of platelet microparticles in AMI was positively associated with the extent of myocardial damage (peak CK-MB: r = 0.408, p = 0.019 and peak GOT: r = 0.384, p = 0.026). CONCLUSIONS: The number of platelet microparticles was increased in AMI as compared to unstable angina and associated with the extent of myocardial damage.

On-admission High Neutrophil to Lymphocyte Ratio as Predictor of In-hospital Adverse Cardiac Event in ST-elevation Myocardial Infarction.

AIM: to investigate the role of neutrophil-to-lymphocyte ratio (NLratio) in predicting in-hospital adverse cardiac events in patients with STEMI. METHODS: this was a cohort study on patients with STEMI onset 24 hour hospitalised in ICCU. NLratio was calculated as absolute neutrophil count divided with lymphocyte count measured by automated blood cell counter on admission.The outcome was in-hospital adverse cardiac events, which were recorded during follow-up. The cut-off value of NLratio to predict outcome was determined by ROC curve analysis. Univariate and multivariable analysis to assess whether high NLratio was independent predictor for in-hospital adverse events were performed. RESULTS: among 165 subjects, in-hospital adverse cardiac events occurred in 49 subjects (29%). The cut-off value of NLratio was 6.2. The univariate analysis showed that NLratio >6.2 had an odd ratio of 3.19 (95% CI 1.55-6.55, p=0.002) to develop in-hospital adverse cardiac events. The multivariate analysis showed that NLratio was an independent predictor of in-hospital adverse cardiac events with an odd ratio of 4.10 (95% CI 1.59-10.54, p=0.003). CONCLUSION: high on-admission NLratio is an independent predictor for in-hospital adverse cardiac events in patients hospitalised for STEMI.

Local and global processing in blind and sighted children in a naming and drawing task.

This study investigated the spatial analysis of tactile hierarchical patterns in 110 early-blind children aged 6-8 to 16-18 years, as compared to 90 blindfolded sighted children, in a naming and haptic drawing task. The results revealed that regardless of visual status, young children predominantly produced local responses in both tasks, whereas the production of integrated responses emerged later. Development of local and global processing seems to proceed similarly in the two populations, but local processing continued to occur at high levels over a larger age range in the blind. The possibility of visual mediation is pointed out, as totally blind children tended to process information locally more often than blind children with minimal light perception.

How explicit and implicit test instructions in an implicit learning task affect performance.

Typically developing children aged 5 to 8 years were exposed to artificial grammar learning. Following an implicit exposure phase, half of the participants received neutral instructions at test while the other half received instructions making a direct, explicit reference to the training phase. We first aimed to assess whether implicit learning operated in the two test conditions. We then evaluated the differential impact of age on learning performances as a function of test instructions. The results showed that performance did not vary as a function of age in the implicit instructions condition, while age effects emerged when explicit instructions were employed at test. However, performance was affected differently by age and the instructions given at test, depending on whether the implicit learning of short or long units was assessed. These results suggest that the claim that the implicit learning process is independent of age needs to be revised.

Children's spatial analysis of hierarchical patterns: construction and perception.

Two experiments were reported that aimed at investigating the development of spatial analysis of hierarchical patterns in children between 3 and 9 years of age. A total of 108 children participated in the drawing experiment, and 224 children were tested in a force-choice similarity judgment task. In both tasks, participants were exposed to consistent and inconsistent targets for short (300-ms) and long (3-s) durations. The drawing task showed that 3-year-old children either preferred to draw the local level or reproduced both levels in a nonintegrated manner. Coordination between the 2 processes started to emerge at 4 years of age, and 6-year-old children produced essentially correct integrated responses. The similarity judgment task confirmed that local processing dominated at 3 years of age. Preference for global processing appeared at 5 years of age, and it gained in strength later. Significant effects of stimulus consistency and stimulus duration were also found. In particular, the use of inconsistent patterns in the similarity judgment task revealed a phenomenon of local-to-global interference in the 3-year-olds.