Rapid weight gain in early life is associated with severity of respiratory syncytial virus (RSV) bronchiolitis in children.

OBJECTIVES: This study aimed to investigate whether rapid weight gain in early life was associated with the severity of respiratory syncytial virus (RSV) bronchiolitis in children. METHODS: We retrospectively reviewed 190 patients (1-24 months) hospitalized for RSV bronchiolitis. Parameters of bronchiolitis severity were compared between rapid (change in weight z-score from birth >0.67, n = 65) and normal weight gain groups (n = 125). We assessed for correlations between bronchiolitis severity and weight gain. Linear regression was performed to predict for bronchiolitis severity based on weight gain, controlling for covariates. SPSS was used for statistical analyses. RESULTS: The rapid weight gain group had longer mean durations of tachypnea (2.3±2.0 vs. 1.7±1.8 days, P = 0.027), wheezing (3.2±2.5 vs. 1.6±1.8 days, P < 0.001), and chest retractions (1.5±2.2 vs. 0.6±1.3 days, P = 0.007). Correlations of weight gain with tachypnea (r = 0.146), wheezing (r = 0.279), and chest retractions (r = 0.179) were statistically significant. Weight gain predicted for tachypnea (B = 0.485, P = 0.013) and wheezing (B = 0.846, P = 0.001) durations after adjusting for covariates of severity (age, sex, current weight, RSV type, coinfection, recurrent bronchiolitis, hospital stay, fever, oxygen supplementation, maximal respiratory and heart rates, and laboratory indices). CONCLUSIONS: Our findings suggest an association between weight gain and severity of RSV bronchiolitis in young children. Weight gain was significantly associated with the durations of tachypnea and wheezing. The trajectory of weight gain in early life may play a significant role in the clinical course of RSV bronchiolitis.

Genetic polymorphism of SMAD5 is associated with Kawasaki disease.

Mothers against decapentaplegic homolog (SMAD) proteins are intracellular mediators of members of the transforming growth factor-ß (TGF-ß) superfamily, which are activated by bone morphogenetic proteins (BMPs). On activation, SMAD5 forms heterometric SMAD complexes, which are translated to the nucleus where they regulate gene transcription. TGF-ß induces T cell activation and cardiovascular disease, two important features of Kawasaki disease (KD), whereas BMP is associated with coronary artery disease. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) of SMAD5 may be associated with KD and coronary arterial lesions (CALs). Genotyping for 15 SNPs of the SMAD5 gene (rs3764941, rs10085013, rs6596284, rs7356756, rs13179769, rs13166063, rs1109158, rs4585442, rs4146185, rs12719481, rs6865297, rs3206634, rs6871224, rs1057898, and rs7031) was performed by direct sequencing of 105 KD patients and 303 healthy adult controls. We also compared the allele frequencies between a CAL group (n = 31) and a normal coronary group (n = 74). Results showed that among the 15 SNPs, rs3206634 was significantly associated with KD in a recessive model (odds ratio = 2.31, p = 0.019), whereas there was no association between any of the 15 SNPs and CALs. These findings may be used as a risk factors development of KD or for future generations of therapeutic treatments for KD.

N-terminal pro-brain natriuretic peptide (NT proBNP) as a predictive indicator of initial intravenous immunoglobulin treatment failure in children with Kawasaki disease: a retrospective study.

Intravenous immunoglobulin (IVIG) administered in the acute stage of Kawasaki disease (KD) is the standard therapy. Few reports describe nonresponders to initial treatment with IVIG in KD, which remains the most consistent risk factor for coronary artery lesions (CALs). This study aimed to investigate whether the serum level of N-terminal pro-brain natriuretic peptide (NT-proBNP) can be a predictive indicator for identifying patients with KD at higher risk of IVIG treatment failure. In this study, 135 patients with a diagnosis of KD admitted for IVIG treatment were retrospectively enrolled for analysis. Of these 135 patients, 22 were nonresponders who received additional rescue therapy because they had an elevated body temperature 36 h after completion of initial IVIG treatment. The NT-proBNP concentration was significantly higher in the nonresponder group (2,465.36 ± 3,293.24 pg/mL) than in the responder group (942.38 ± 1,293.48 pg/mL) (p < 0.05). The optimal sensitivity and specificity cutoff point for predicted nonresponders was 1,093.00 pg/mL or higher. The sensitivity and specificity for prediction of IVIG response were respectively 70.0 and 76.5 %. The findings show that NT-proBNP is a helpful marker in determining patients at risk for not responding to initial IVIG treatment. The authors suggest that patients with an NT-proBNP level of 1,093.00 pg/dL or higher are likely to fail initial IVIG and may require further rescue therapy.

Children with transient loss of consciousness: Clinical characteristics and the effectiveness of diagnostic tests.

BACKGROUND: Transient loss of consciousness (TLOC) is common among children and adolescents. The aims of this study were to identify clinical differences between patients with vasovagal syncope and those with epileptic seizures, which account for a large proportion of TLOC cases, and to evaluate the effectiveness of various diagnostic tests. METHODS: The medical records of 160 children and adolescents with TLOC were analyzed retrospectively, and age, sex, clinical symptoms, and trigger factors were recorded. The cardiological and neurological evaluations performed included electrocardiograms, computed tomography scanning, magnetic resonance imaging, electroencephalograms (EEGs), echocardiograms, and head-up tilt tests (HUTTs). Overall assessments of the 160 patients generated final diagnoses. RESULTS: The mean age of patients was 14.6 years old and TLOC occurred more frequently among girls (59.4%). The most common final diagnosis was vasovagal syncope (n = 102, 63.4%), followed by undetermined (n = 21, 13.1%) and epileptic seizures (n = 17, 10.6%). There were many other diagnoses, including cardiogenic syncope (1.3%). Patients diagnosed with vasovagal syncope were much more likely to have dizziness or light-headedness and blurred vision as pre-symptoms (p < 0.05), whereas patients diagnosed with epileptic seizures were more likely to have convulsions as an accompanying sign (p < 0.05). In addition, standing up was the most significant trigger factor for TLOC among those diagnosed with vasovagal syncope (p < 0.05). The sensitivity, specificity, and accuracy of the HUTT for vasovagal syncope were 95.1%, 75.0%, and 91.8%, respectively. Similarly, the sensitivity, specificity, and accuracy of EEGs for epileptic seizures were 80.0%, 70.6%, and 80.0%, respectively. CONCLUSION: Vasovagal syncope and epileptic seizures should be considered as possible causes of most cases of TLOC in children and adolescents. An accurate case history and appropriate evaluation are essential for correct diagnoses.

Epidemiology of Kawasaki Disease in South Korea: A Nationwide Survey 2015-2017.

BACKGROUND: This study aimed to investigate recent epidemiologic features of Kawasaki disease (KD) in South Korea. METHODS: The ninth triennial nationwide questionnaire survey collected data on the demographic findings, symptoms and signs, treatment patterns and coronary artery complications of acute-phase KD occurred in 2015-2017 from 98 hospitals with pediatric residency programs and 108 community hospitals without residency programs. RESULTS: We received data from 93 of the 98 hospitals (response rate: 94.9%) with residency programs and 75 of the 108 community-based children's hospitals (response rate: 69.4%) without residency programs. In the 3-year survey period, a total of 15,378 (5449 in 2015, 5171 in 2016 and 4758 in 2017) cases of KD were reported. The mean age at diagnosis was 33.0 ± 24.8 months (range: 0-205 months), and the male-to-female ratio was 1.41:1. The overall KD incidence was 196.9 (202.2 in 2015, 197.1 in 2016 and 191.0 in 2017) per 100,000 younger than 5 years population. Recurrent cases were 4.85%. KD occurred more frequently during winter (December-January) and late spring (May-June). Intravenous immunoglobulin (IVIG) was administered to 95% of the patients; nonresponder rate for the first IVIG was 14.8%. Coronary artery aneurysms and giant coronary artery aneurysms (internal diameter >8 mm) occurred in 1.7% and 19 patients, respectively. Two patients died due to multiorgan failure and hepatic encephalopathy. CONCLUSION: Peak incidence of KD in South Korea was 202.2 per 100,000 younger than 5 years population (2015), and the incidence of giant coronary artery aneurysm decreased to 0.09% (2017).

Photovoltaic characteristics of polymer solar cells fabricated by pre-metered coating process.

We present the results of a study of flat and uniform poly(3-hexylthiophene):methanofullerene bulk-heterojunction photovoltaic (PV) layers that were produced by a simple pre-metered horizontal-dipping process for the fabrication of polymer solar cells (PSCs). It is shown that this process can produce high quality and thin films by utilizing the downstream meniscus of the solution, which can be controlled by adjusting experimental parameters of the gap height and the carrying speed. It is also shown that the produced PV film exhibits high power conversion efficiency of ca. 4.2% with a large active area. It was demonstrated that this pre-metered process for solution coating may be promising for achieving highly efficient, reliable, and large-area PSCs.

Organic light-emitting devices fabricated using a premetered coating process.

We present the results of a study of flat and uniform organic electroluminescent (EL) layers produced using a simple premetered horizontal-dipping process. It is shown that this process can produce high quality organic semiconductor thin films by utilizing the downstream meniscus of the solution, which may be controlled by adjusting the gap height and the carrying speed. It is also shown that the organic light emitting devices (OLEDs) produced using this method exhibit a peak brightness in excess of 52,000 cd/m(2) and a maximum efficiency of 24 cd/A, with a large active area. From these results, we show that this premetered process for solution coating offers considerable promise for the production of highly efficient, reliable, and large-area solution-processed OLEDs.

Polarized organic light-emitting device on a flexible giant birefringent optical reflecting polarizer substrate.

We present the results of a study of highly linear polarized light emissions from an Organic Light-Emitting Device (OLED) that consisted of a flexible Giant Birefringent Optical (GBO) multilayer polymer reflecting polarizer substrate. Luminous Electroluminescent (EL) emissions over 4,500 cd/m(2) were produced from the polarized OLED with high peak efficiencies in excess of 6 cd/A and 2 lm/W at relatively low operating voltages. The direction of polarization for the emitted EL light corresponded to the passing (ordinary) axis of the GBO-reflecting polarizer. Furthermore, the estimated polarization ratio between the brightness of two linearly polarized EL emissions parallel and perpendicular to the passing axis could be as high as 25 when measured over the whole emitted luminance range.

High antistreptolysin O titer is associated with coronary artery lesions in patients with Kawasaki disease.

PURPOSE: In Kawasaki disease (KD) patients, coronary artery complications, incomplete and refractory types occur more frequently in patients with streptococcal or other bacterial/viral infections. Recently, we observed a higher incidence of coronary lesions in KD patients with high anti-streptolysin O (ASO) titer. Therefore, we hypothesized that KD patients diagnosed with concurrent streptococcal infection have poor prognosis, with respect to treatment response and development of coronary artery lesions. METHODS: A retrospective review was performed in 723 patients with KD who were admitted to 2 major hospitals between June 2010 and September 2017. RESULTS: Among 723 patients with KD, 11 initially showed an elevated ASO titer (>320 IU/mL) or elevated follow-up ASO titer after treatment. Of these patients, 5 showed no response to the first intravenous immunoglobulin treatment, 3 had abnormalities of the coronary arteries. This is a significantly higher proportion of patients with a high ASO titer (n=3, 27.3%) than those with a normal ASO titer (n=53, 7.4%; P=0.047). A severe clinical course was seen in 81.8% of patients in the high ASO group versus 14.5% of patients in the normal ASO group. CONCLUSION: It is not certain whether acute streptococcal infection may cause KD, but this study revealed that KD with high ASO titers showed higher rates of severe clinical course. It may be helpful to analyze concurrent streptococcal infection in patients with a severe clinical course.

An infant presenting with Kawasaki disease following immunization for influenza: A case report.

Kawasaki disease (KD) is a childhood vascular disorder of unknown etiology. Concerns have recently been raised regarding vaccinations as a potential risk factor for KD. In addition, various forms of vasculitis have been reported as adverse events following administration after various vaccines. Patients exhibiting post vaccination KD have previously been described; however, thus far, to the best of our knowledge, only one patient exhibiting post influenza vaccination KD has been reported in Japan. The present study describes a case of KD 24 h after immunization with influenza in an infant (age, 18 months) following 6 days of high fever, a body rash that had persisted for 2 days and nonsuppurative bilateral conjunctivitis. To the best of the authors' knowledge, this is the first reported case in Korea and the present study reviews various recent studies regarding vasculitis following vaccination and the causal association between them.

Mycoplasma Infection as a cause of Persistent Fever after Intravenous Immunoglobulin Treatment of Patients with Kawasaki Disease: Frequency and Clinical Impact.

BACKGROUND: Mycoplasma is a common cause of respiratory infections and may require differential diagnosis from Kawasaki disease (KD). In this study, we investigated the frequency and clinical manifestations of mycoplasma infection in patients with KD. MATERIALS AND METHODS: Medical records of 375 in-patients admitted for treatment during the acute stage of KD, were collected, and reviewed retrospectively. Of these patients, 152 (40.5%) were also tested for recent mycoplasma infection. Patients with positive results (anti-mycoplasma IgM Ab >1:640 or cold agglutinin >1:64) were designated as the case group (n = 37, 24.3%) whereas those with negative results were designated as the control group (n = 115, 75.7%). Clinical findings of the two groups were compared. RESULTS: Patients in the case group were older than those in the control group (mean age, 48.2 ± 32.1 months, vs. 31.7 ± 21.7 months; P = 0.001). There were significant differences between the case and control groups in the changes in the extremities (78.3% vs. 57.4%, respectively; P = 0.031), and in fever duration (6.5 ± 2.5 days vs. 5.4 ± 1.5 days; P = 0.047). Of the 37 patients with positive mycoplasma testing, 7 (18.9%) had persistent fever even after the symptoms and signs of systemic inflammation (acute phase of KD) had been resolved. These patients were positive for mycoplasma infection during further evaluation of persistent fever, and all of them responded to macrolide antibiotics. CONCLUSIONS: We found that mycoplasma infection is somewhat related to KD. When fever persists after resolution of the acute stage of KD, mycoplasma infection may be considered as a possible cause of fever in preschool-aged children.

Multicenter, Single-Arm, Phase IV Study of Combined Aspirin and High-Dose "IVIG-SN" Therapy for Pediatric Patients with Kawasaki Disease.

BACKGROUND AND OBJECTIVES: Intravenous immunoglobulin-SN (IVIG-SN) is a new human immunoglobulin product. Its safety is ensured by pathogen-elimination steps comprising solvent/detergent treatment and a nanofiltration process. This multicenter clinical study was designed to evaluate the efficacy and safety of combined aspirin and high-dose IVIG-SN therapy in pediatric patients with Kawasaki disease (KD). SUBJECTS AND METHODS: We evaluated coronary artery lesions (CALs) at 2 and 7 weeks after administering IVIG-SN; total fever duration; and variations in erythrocyte sedimentation rate, N-terminal pro B-type natriuretic peptide or B-type natriuretic peptide, and creatine kinase-myocardial band level before and after treatment with IVIG-SN (2 g/kg). Adverse events were monitored. RESULTS: Forty-five patients were enrolled, three of whom were excluded according to the exclusion criteria; the other 42 completed the study. The male:female ratio was 0.91:1, and the mean age was 29.11±17.23 months. The mean fever duration before IVIG-SN treatment was 6.45±1.30 days. Although most patients had complete KD (40 patients, 90.91%), four had atypical KD (9.09%). After IVIG-SN treatment, one patient (2.38%) had CALs, which was significantly lower than the incidence reported previously (15%) (p=0.022), but not significantly different from recent data (5%). There were no serious adverse events, though 28 patients (63.64%) had mild adverse events. Three adverse drug reactions occurred in 2 patients (eczema, anemia, and increased eosinophil count), all of which were transient. CONCLUSION: IVIG-SN treatment in patients with KD was safe and effective.

The Therapeutic Effect of PLAG against Oral Mucositis in Hamster and Mouse Model.

Chemotherapy-induced mucositis can limit the effectiveness of cancer therapy and increase the risk of infections. However, no specific therapy for protection against mucositis is currently available. In this study, we investigated the therapeutic effect of PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride) in 5-fluorouracil (5-FU)-induced oral mucositis animal models. Hamsters were administered 5-FU (80 mg/kg) intraperitoneally on days 0, 6, and 9. The animals' cheek pouches were then scratched equally with the tip of an 18-gage needle on days 1, 2, and 7. PLAG was administered daily at 250 mg/kg/day. PLAG administration significantly reduced 5-FU/scratching-induced mucositis. Dramatic reversal of weight loss in PLAG-treated hamsters with mucositis was observed. Histochemical staining data also revealed newly differentiated epidermis and blood vessels in the cheek pouches of PLAG-treated hamsters, indicative of recovery. Whole blood analyses indicated that PLAG prevents 5-FU-induced excessive neutrophil transmigration to the infection site and eventually stabilizes the number of circulating neutrophils. In a mouse mucositis model, mice with 5-FU-induced disease treated with PLAG exhibited resistance to body-weight loss compared with mice that received 5-FU or 5-FU/scratching alone. PLAG also dramatically reversed mucositis-associated weight loss and inhibited mucositis-induced inflammatory responses in the tongue and serum. These data suggest that PLAG enhances recovery from 5-FU-induced oral mucositis and may therefore be a useful therapeutic agent for treating side effects of chemotherapy, such as mucositis and cachexia.

Rapid weight gain in early life is associated with severity of respiratory syncytial virus (RSV) bronchiolitis in children

Objectives This study aimed to investigate whether rapid weight gain in early life was associated with the severity of respiratory syncytial virus (RSV) bronchiolitis in children. Methods We retrospectively reviewed 190 patients (1–24 months) hospitalized for RSV bronchiolitis. Parameters of bronchiolitis severity were compared between rapid (change in weight z-score from birth >0.67, n = 65) and normal weight gain groups (n = 125). We assessed for correlations between bronchiolitis severity and weight gain. Linear regression was performed to predict for bronchiolitis severity based on weight gain, controlling for covariates. SPSS was used for statistical analyses. Results The rapid weight gain group had longer mean durations of tachypnea (2.3±2.0 vs. 1.7±1.8 days, P = 0.027), wheezing (3.2±2.5 vs. 1.6±1.8 days, P < 0.001), and chest retractions (1.5±2.2 vs. 0.6±1.3 days, P = 0.007). Correlations of weight gain with tachypnea (r = 0.146), wheezing (r = 0.279), and chest retractions (r = 0.179) were statistically significant. Weight gain predicted for tachypnea (B = 0.485, P = 0.013) and wheezing (B = 0.846, P = 0.001) durations after adjusting for covariates of severity (age, sex, current weight, RSV type, coinfection, recurrent bronchiolitis, hospital stay, fever, oxygen supplementation, maximal respiratory and heart rates, and laboratory indices). Conclusions Our findings suggest an association between weight gain and severity of RSV bronchiolitis in young children. Weight gain was significantly associated with the durations of tachypnea and wheezing. The trajectory of weight gain in early life may play a significant role in the clinical course of RSV bronchiolitis (AU)

Cloning and characterization of the rat Hsf2 promoter: a critical role of proximal E-box element and USF protein in Hsf2 regulation in different compartments of the brain.

The complex patterns of tissue-, cell type- and developmental stage-specific expression of heat shock factor 2 (Hsf2) raise a question of how this can be achieved for this ubiquitous transcription factor. To explore molecular mechanisms responsible for the regulated expression of Hsf2, a 2638-bp 5'-flanking region of the rat Hsf2 gene was cloned and characterized. Since the brain represents one of the most complicated organs composed of several regions with different cell types, differential regulation of Hsf2 in various brain regions was investigated in detail. Results show that the major transcription initiation site of the Hsf2 gene is located at cytosine-155 relative to the translation initiation site. The E-box element located immediate upstream of the transcription initiation site was demonstrated to be critical for Hsf2 promoter activity, and the upstream stimulatory factor (USF) protein was identified as the major E-box binding protein. That the only two base exchange of the E-box core sequences from CACGTG to CACGGT severely impaired Hsf2 promoter activity and completely eliminated USF binding clearly demonstrated that the specific binding of USF to E-box is critical for Hsf2 promoter activity. Here we demonstrated that the Hsf2 expression levels varied significantly in different brain regions. We also demonstrated that Hsf2 expression levels in various brain regions relatively correlated with the E-box binding activity of USF. Based on these results, we suggest that E-box binding activity of USF protein may act as one of the major regulators of Hsf2 expression in situ although a possible involvement of other transcription factors cannot be ruled out. The presence of several transcription factor binding sites of biological importance in the Hsf2 promoter suggests that identifying the interplay of USF and these factors should help further elucidate the molecular mechanisms of tissue-, cell type- and developmental stage-specific expression of Hsf2.

Negative regulatory role of overexpression of PLC gamma 1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts.

The early growth response 1 (Egr-1) gene product is a transcription factor that functions as an oikis factor. Loss of Egr-1 expression is closely associated with tumor formation. Phospholipase Cgamma1 (PLCgamma1) is overexpressed in some tumors, and its overexpression causes anchorage-independent growth. Here we report that overexpression of PLCgamma1 and SH2-SH3 domain of PLCgamma1 decreased induction of Egr-1 and the Egr-1-regulated genes TSP-1 and PAI-1. Results from the nuclear run-on assay and transfection experiment with the proximal 455 base pair region of the Egr-1 promoter (-454 to +1) showed that Egr-1 transcriptional activity was suppressed in PLCgamma1-3Y1 cells whereas decay of Egr-1 mRNA was similar in both cell lines. Serum response element- and ternary complex factor Elk-1-mediated transcriptional activation of the reporter gene in response to EGF were also inhibited in PLCgamma1-3Y1 cells. Pretreatment with the protein synthesis inhibitor cycloheximide (CHX) partially abrogated the serum-induced suppression of Egr-1 transcription in PLCgamma1-3Y1 cells, suggesting that a CHX-sensitive factor(s) is involved in the suppression of Egr-1 transcription in PLCgamma1-3Y1 cells. Our results demonstrated that overexpression of PLCgamma1 functions as a negative modulator of the tumor suppressor Egr-1 gene expression, possibly through inhibition of Elk-1-dependent transcriptional activity.

Inhibition of Shc/Grb2 protein-protein interaction suppresses growth of B104-1-1 tumors xenografted in nude mice.

Actinomycin D was revealed as an inhibitor of Shc/Grb2 interaction in cell lines from our recent study. Shc and Grb2 proteins are important molecules in Ras signaling pathways leading to cellular differentiation and proliferation, which require dramatic morphological changes. It was detected by transmission electron microscopy that actinomycin D induced significant changes in cellular ultrastructures of B104-1-1 cells and confirmed that the changes were due to inhibition of Shc/Grb2 interaction by actinomycin D rather than its inhibitory effect on transcription. Because actinomycin D was dispersed mainly in cytoplasm and Shc peptide (synthetic 13 amino acid tyrosine phosphorylated polypeptide) successfully displaced actinomycin D binding to its cellular targets while the other polypeptide from PDGF receptor could not. We examined the effect of actinomycin D on growth of B104-1-1 tumor xenografted in nude mice. Tumor growth was inhibited in vivo after treatment with this inhibitor. Efficacy was correlated with a reduction in the levels of Shc/Grb2 binding in excised tumors. These results suggest that actinomycin D inhibited Shc/Grb2 interaction in B104-1-1 tumor xenografted in nude mice.