Long-term bidirectional association between asthma and attention deficit hyperactivity disorder: A big data cohort study.

Background: Previous studies have argued that attention deficit hyperactivity disorder (ADHD) is associated with asthma. However, reliable evidence to verify this association has not yet been reported. Objectives: To investigate the bidirectional association between asthma and ADHD through a 12-year big data cohort study. Methods: The independent variable group was extracted from 3.5 million individuals randomly sampled by the National Health Insurance Service (NHIS). In Study 1, the incidence of ADHD according to asthma was evaluated, while in Study 2, the incidence of asthma according to ADHD was analyzed. Propensity score (PS) matching with several variables was used to obtain a control group. Measurements and main results: In Study 1, the asthma group included 131,937 individuals and the non-asthma group included 131,937 individuals. The adjusted hazard ratio (aHR) for ADHD in the asthma group was 1.17 [95% confidence interval (CI): 1.11-1.23]. In subgroup analysis, the aHRs for ADHD of individuals in the subgroups male sex, 0-5 years old, 6-10 years old, atopic dermatitis, allergic rhinitis, Charlson comorbidity index (CCI) 1, and CCI > 2 were significant (aHR: 2.83, 1.70, 1.79, 1.09, 1.15, 1.06, and 1.49, respectively). In Study 2, ADHD was found to significantly affect asthma in all age groups (aHRs of the subgroups 0∼60 and 0∼17 years old were 1.10 and 1.09, respectively). In the 0∼17 years old subgroup, the association of ADHD with asthma was greater with younger age (aHRs of the subgroups 0∼5 and 6∼10 years old were 2.53 and 1.54, respectively). Conclusion: From long-term follow-up, the incidence of ADHD was 1.17 times higher in the asthma group than in the control group. The incidence of asthma was 1.10 times higher in the ADHD group than in the control group. Asthma and ADHD have a bidirectional relationship, and childhood asthma and ADHD should be rigorously managed.

Isolation and Expression Profile of the Ca-Activated Chloride Channel-like Membrane Protein 6 Gene in Xenopus laevis.

To clone the first anion channel from Xenopus laevis (X. laevis), we isolated a calcium-activated chloride channel (CLCA)-like membrane protein 6 gene (CMP6) in X. laevis. As a first step in gene isolation, an expressed sequence tags database was screened to find the partial cDNA fragment. A putative partial cDNA sequence was obtained by comparison with rat CLCAs identified in our laboratory. First stranded cDNA was synthesized by reverse transcription polymerase-chain reaction (RT-PCR) using a specific primer designed for the target cDNA. Repeating the 5' and 3' rapid amplification of cDNA ends, full-length cDNA was constructed from the cDNA pool. The full-length CMP6 cDNA completed via 5'- and 3'-RACE was 2,940 bp long and had an open reading frame (ORF) of 940 amino acids. The predicted 940 polypeptides have four major transmembrane domains and showed about 50% identity with that of rat brain CLCAs in our previously published data. Semi-quantification analysis revealed that CMP6 was most abundantly expressed in small intestine, colon and liver. However, all tissues except small intestine, colon and liver had undetectable levels. This result became more credible after we did real-time PCR quantification for the target gene. In view of all CLCA studies focused on human or murine channels, this finding suggests a hypothetical protein as an ion channel, an X. laevis CLCA.

Cloning and heterologous expression of new xANO2 from Xenopus laevis.

We have successfully isolated a novel anoctamin (xANO2), Ca(2+)-activated chloride channel (ANO1, TMEM16A), from Xenopus laevis. The cDNA sequence was determined to belong to the anoctamin family by comparison with the xTMEM16A sequence in a previous report. Full length cDNA synthesis was performed by repeating 5'- and 3'-rapid amplification of cDNA end (RACE). We successfully completed the entire cDNA sequence and transiently named this sequence xANO2. The xANO2 cDNA is 3884 base pair (bp) long and codes 980 amino acid (aa) proteins. According to an aa homology search using the Basic Local Alignment Search Tool (BLAST), xANO2 showed an overall identity of 92% to xTMEM16A (xANO1) independently sub-cloned in our laboratory. A primary sequence of xANO2 revealed typical characteristics of transmembrane proteins. In tissue distribution analysis, the gene products of anoctamins were ubiquitously detected by real-time PCR (RT-PCR). The expression profiles of each anoctamin were different among brain, oocytes, and digestive organs with relatively weak expression. To clarify the anoctamin activity, physiological studies were performed using the whole cell patch-clamp technique with HEK293T cells, enhanced green fluorescent protein (EGFP), and expression vectors carrying anoctamins. Characteristics typical of voltage-dependent chloride currents were detected in cells expressing both xANO2 and xTMEM16A but not with EGFP alone. Sensitive reactions to the anion channel blocker niflumic acid (NFA) were also revealed. Considering these results, xANO2 was regarded as a new TMEM16A belonging to the Xenopus anoctamin family.

Coronary Blood Flow Velocity and Coronary Flow Reserve in Normal Left anterior Descending Coronary Arteries

BACKGROUND: Recently, assessment of left anterior descending (LAD) coronary flow by transthorasic Doppler echocardiography (TTDE) has been emerged as a useful tool in evaluation of microcirculatory function of coronary circulation. The measuring site of coronary flow by TTDE is distal LAD. But it was not fully investigated whether the distal flow velocity is identical to that of proximal segment. The purpose of this study is to compare coronary blood flow velocity and coronary flow reserve (CFR) in normal LAD according to its level. METHOD: 9 patients (1 male, 8 females; mean age 52.8+/-11.1years) were included for this study. Coronary flow velocity was measured with intracoronary Doppler guide wire at the proximal (before first diagonal branch), mid (after second diagonal branch), and distal segments of LAD at baseline and after intracoronary bolus injection of 18 microgram adenosine. Baseline and hyperemic average peak velocity (APV) and CFR were compared between segment. RESULTS: Baseline and hyperemic APV appears to be diminished from proximal (24.6+/-3.5 cm/sec, 55.8+/-10.7 cm/sec) to distal (21.7+/-6.9 cm/sec, 49.7+/-17.2 cm/sec) LAD without statistical significance. But, CFR showed no significant difference in each segments (proximal, mid, and distal segment; 2.3+/-0.26, 2.3+/-0.32, 2.3+/-0.48, p=0.95). As the increment of peak systolic velocity (PSV) from baseline to hyperemic state was larger than that of peak diastolic velocity (PDV), diastolic to peak systolic velocity ratio (DSVR) was decreased significantly by hyperemic state in proximal and distal segment (baseline; 2.1+/-0.8, 2.1+/-0.5 vs hyperemia; 1.8+/-0.6, 1.7+/-0.3, p<0.05). CONCLUSION: Coronary blood flow velocity appears to be decreased from proximal to distal segment of normal LAD without statistical significance. There were no differences in CFR between proximal, mid and distal segment of normal LAD.