Effectiveness of case isolation and class suspension in mitigation of enterovirus transmission in children.

BACKGROUND: Appropriate mitigation strategy to minimize enterovirus (EV) transmission among children is essential to control severe EV epidemics. Scientific evidence for the effectiveness of case isolation and class suspension is lacking. METHODS: EV-infected children ≤ eight years are asked to stay at home for seven days. Classes were suspended for seven days if there are more than two classmates having an onset of herpangina or hand, foot, and mouth disease in one classroom within one week. Study subjects are divided into two groups, group A with class suspension for one week and group B without class suspension. RESULTS: Among 4153 reported EV-infected children from 1085 classes in May and June, 2015 were enrolled. Median incidence of EV infection in a class was 7% (range 3% -60%). The incidence was higher in group A (median 14%, range 3-60%) than that in group B (median 6%, range 3-80%) (P < 0.01). The median incidence is highest in day care center (20%), followed by kindergarten (8%), and primary school (4%) (P < 0.01). Most secondary cases in group A appeared within seven days after the disease onset of index case in the same class. The incidence of EV infection remained low and was similar between the two groups eight days and beyond after the disease onset of index cases. CONCLUSIONS: Targeted class suspension for seven days with case isolation for seven days is an effective measure to mitigate transmission of EV infection in children.

Indoxyl Sulfate Elevated Lnc-SLC15A1-1 Upregulating CXCL10/CXCL8 Expression in High-Glucose Endothelial Cells by Sponging MicroRNAs.

Cardiovascular disease (CVD) is the leading cause of mortality in diabetes mellitus (DM). Immunomodulatory dysfunction is a primary feature of DM, and the emergence of chronic kidney disease (CKD) in DM abruptly increases CVD mortality compared with DM alone. Endothelial injury and the accumulation of uremic toxins in the blood of DM/CKD patients are known mechanisms for the pathogenesis of CVD. However, the molecular factors that cause this disproportional increase in CVD in the DM/CKD population are still unknown. Since long non-protein-coding RNAs (lncRNAs) play an important role in regulating multiple cellular functions, we used human endothelial cells treated with high glucose to mimic DM and with the uremic toxin indoxyl sulfate (IS) to mimic the endothelial injury associated with CKD. Differentially expressed lncRNAs in these conditions were analyzed by RNA sequencing. We discovered that lnc-SLC15A1-1 expression was significantly increased upon IS treatment in comparison with high glucose alone, and then cascaded the signal of chemokines CXCL10 and CXCL8 via sponging miR-27b, miR-297, and miR-150b. This novel pathway might be responsible for the endothelial inflammation implicated in augmenting CVD in DM/CKD and could be a therapeutic target with future clinical applications.

Pectoral Fin Anomalies in tbx5a Knockdown Zebrafish Embryos Related to the Cascade Effect of N-Cadherin and Extracellular Matrix Formation.

Functional knockdown of zebrafish tbx5a causes hypoplasia or aplasia of pectoral fins. This study aimed to assess developmental pectoral fin anomalies in tbx5a morpholino knockdown zebrafish embryos. The expression of cartilage-related genes in the tbx5a morphant was analyzed by DNA microarray, immunostaining, and thin-section histology to examine the detailed distribution of the extracellular matrix (ECM) during different pectoral fin developmental stages. Chondrogenic condensation (CC) in the tbx5a morpholino knockdown group was barely recognizable at 37 h postfertilization (hpf); the process from CC to endoskeleton formation was disrupted at 48 hpf, and the endoskeleton was only loosely formed at 72 hpf. Microarrays identified 18 downregulated genes in tbx5a-deficient embryos, including 2 fin morphogenesis-related (cx43, bbs7), 4 fin development-related (hoxc8a, hhip, axin1, msxb), and 12 cartilage development-related (mmp14a, sec23b, tfap2a, slc35b2, dlx5a, dlx1a, tfap2b, fmr1, runx3, cdh2, lect1, acvr2a, mmp14b) genes, at 24 and 30 hpf. The increase in apoptosis-related proteins (BAD and BCL2) in the tbx5a morphant influenced the cellular component of pectoral fins and resulted in chondrocyte reduction throughout the different CC phases. Furthermore, tbx5a knockdown interfered with ECM formation in pectoral fins, affecting glycosaminoglycans, fibronectin, hyaluronic acid (HA), and N-cadherin. Our results provide evidence that the pectoral fin phenotypic anomaly induced by tbx5a knockdown is related to disruption of the mesoderm and ECM, consequently interfering with mesoderm migration, CC, and subsequent endoskeleton formation.

Anti-apoptotic effects of IGF-I on mortality and dysmorphogenesis in tbx5-deficient zebrafish embryos.

BACKGROUND: Tbx5 deficiency in zebrafish causes several abnormal phenotypes of the heart and pectoral fins. It has been reported that exogenous human growth hormone can enhance expression of downstream mediators in the growth hormone and insulin-like growth factor I (IGF-I) pathway and partially restore dysmorphogenesis in tbx5 morphants. This study aimed to further evaluate the effects of IGF-I on cell apoptosis and dysmorphogenesis in zebrafish embryos deficient for tbx5. RESULTS: Among the five studied groups of zebrafish embryos (wild-type embryos [WT], tbx5 morphants [MO], mismatched tbx5 morpholino-treated wild-type embryos [MIS], IGF-I-treated wild-type embryos [WTIGF1], and IGF-I-treated tbx5 morphants [MOIGF1]), the expression levels of the ifg1, igf1-ra, ifg-rb, erk1, and akt2 genes as well as the ERK and AKT proteins were significantly reduced in the MO group, but were partially restored in the MOIGF1 group. These expression levels remained normal in the WT, MIS, and WTIGF1 groups. Exogenous human IGF-I also reduced the incidence of phenotypic anomalies, decreased the expression levels of apoptotic genes and proteins, suppressed cell apoptosis, and improved survival of the MOIGF1 group. CONCLUSIONS: These results suggest that IGF-I has an anti-apoptotic protective effect in zebrafish embryos with tbx5 deficiency.

Self-sampling HPV test in women not undergoing Pap smear for more than 5 years and factors associated with under-screening in Taiwan.

BACKGROUND/PURPOSE: Under-utilization of Papanicolaou (Pap) smear causes a gap in the prevention of cervical neoplasms. A prospective population-based study was conducted investigating whether a self-sampling human papillomavirus (HPV) test was feasible for under-users of Pap smear and factors associated with under-screening in Taiwan. METHODS: Women not having Pap smear screening for > 5 years were invited to participate in this study. Invitation letters and educational brochures were mailed to 4% of randomly selected eligible women from Taoyuan City, Taiwan, and responders received an HPV self-sampling kit. Those with HPV-positive results were recalled for a Pap smear and colposcopy. RESULTS: Between March 2010 and June 2012, 10,693 women were invited, 354 responded (3.3%), and 282 (2.6%) gave valid informed consent, answered the questionnaire, and submitted HPV samples. The median age of enrolled women was 48.1 years. Forty-seven women (16.7%) had a positive HPV test, and 14 women accepted further survey to find two CIN2+. Another two cases of CIN2+ were identified from a national registry database. The cost of direct mailing self-samplers was less than that done on request (from NT$434,866 to NT$164,229, response rate of 5% to 15%, respectively, versus NT$683,957 for detecting 1 CIN2+). Reasons for not attending screening included lack of time, embarrassment, assumed low risk, fear of positive results, and perceived potential pain. Among the responders, 90.8% found the method acceptable. CONCLUSION: Our study indicated that different approaches (e.g., direct mailing self-samplers to under-users and/or various educational interventions) must be explored to improve coverage in populations with culture characteristics similar to Taiwan.

Incidence and renal survival of ESRD in the young Taiwanese population.

BACKGROUND AND OBJECTIVES: ESRD in the young represents a heavy burden to patients, families, and health care systems. This nationwide retrospective study characterized the incidence of ESRD and analyzed diagnoses associated with renal survival in the young population in Taiwan. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Through use of Taiwan's National Health Insurance Research Database, the population of young patients (age<30 years, including children and young adults) with ESRD between January 1998 and December 2009 were enrolled. The medical claims were used to derive the date when the cause of ESRD was first determined. The medical data were reviewed and the renal survival time (time from first diagnosis of the cause to the start of ESRD) was calculated by experts, including clinical physicians and a large-database specialist. RESULTS: The incidence rate of ESRD in the young population was high compared with the worldwide rate at 21.1 per million person-years, whereas the incidence in the pediatric group was still similar to that in other countries at 10.3 per million person-years. A total of 2304 patients with new-onset ESRD and identified renal diseases during the study period were enrolled. All preschool-age patients (100%) began receiving peritoneal dialysis as their initial treatment for ESRD. The leading causes, which varied by sex and onset age, were glomerulonephropathy followed by hypertension for the young adult group and glomerulonephropathy followed by congenital anomalies of the kidney and urinary tract (CAKUT) for the pediatric group. Renal survival was cause-dependent. The median overall renal survival duration was 0.8 year (interquartile range [IQR], 0.7-3.5 years). CAKUT-related ESRD had the longest progression time (median renal survival, 16.0 years; IQR, 10.7-23.5 years); glomerulonephropathy progressed more rapidly into ESRD and had the shortest median renal survival of 0.5 year (IQR, 0.1-2.7 years). CONCLUSIONS: The incidence and causes of ESRD greatly differ between pediatric patients and young adults. Moreover, renal survival in the young population markedly varies depending on the cause of renal disease.

Otorrhea as a sign of medical treatment failure in acute otitis media: two cases with silent mastoiditis complicated with facial palsy.

We report two children with otitis media who developed facial palsy despite prompt antibiotic therapy. Brain images revealed silent mastoiditis. Persistent otorrhea may be a cautious sign of medical treatment failure or complication of acute otitis media, including mastoiditis or facial palsy. Delayed identification of coexisting mastoiditis or hesitation over surgical intervention may lead to treatment failure and complications. Adequate intravenous antibiotics and myringotomy provide reasonable and appropriate management to prevent permanent sequelae.

The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by tbx5 deficiency in zebrafish (Danio rerio) embryos.

BACKGROUND: Dysmorphogenesis and multiple organ defects are well known in zebrafish (Danio rerio) embryos with T-box transcription factor 5 (tbx5) deficiencies, mimicking human Holt-Oram syndrome. METHODS: Using an oligonucleotide-based microarray analysis to study the expression of special genes in tbx5 morphants, we demonstrated that GH and some GH-related genes were markedly downregulated. Zebrafish embryos microinjected with tbx5-morpholino (MO) antisense RNA and mismatched antisense RNA in the 1-cell stage served as controls, while zebrafish embryos co-injected with exogenous growth hormone (GH) concomitant with tbx5-MO comprised the treatment group. RESULTS: The attenuating effects of GH in tbx5-MO knockdown embryos were quantified and observed at 24, 30, 48, 72, and 96 h post-fertilization. Though the understanding of mechanisms involving GH in the tbx5 functioning complex is limited, exogenous GH supplied to tbx5 knockdown zebrafish embryos is able to enhance the expression of downstream mediators in the GH and insulin-like growth factor (IGF)-1 pathway, including igf1, ghra, and ghrb, and signal transductors (erk1, akt2), and eventually to correct dysmorphogenesis in various organs including the heart and pectoral fins. Supplementary GH also reduced apoptosis as determined by a TUNEL assay and decreased the expression of apoptosis-related genes and proteins (bcl2 and bad) according to semiquantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis, respectively, as well as improving cell cycle-related genes (p27 and cdk2) and cardiomyogenetic genes (amhc, vmhc, and cmlc2). CONCLUSIONS: Based on our results, tbx5 knockdown causes a pseudo GH deficiency in zebrafish during early embryonic stages, and supplementation of exogenous GH can partially restore dysmorphogenesis, apoptosis, cell growth inhibition, and abnormal cardiomyogenesis in tbx5 knockdown zebrafish in a paracrine manner.

Ovarian torsion caused by teratoma masquerading as perforated appendicitis in a 5-year-old girl.

Ovarian torsion is a well-known but poorly recognized disease. Although ovarian torsion is the most common complication of ovarian tumors in children, it is an uncommon cause of abdominal pain in pediatric patients. Ovaries can be only salvaged by prompt diagnosis and timely surgical intervention. Acute ovarian torsion without appropriate treatment may result in loss of ovarian function, tissue necrosis, and death. The objective of this article is to present a case of pediatric ovarian torsion and describe the difficulty of distinguishing it from perforated appendicitis in the emergency department (ED). We report a 5-year-old girl who presented to the ED with nausea, tenderness over the right lower guardant of her abdomen, fever, and anorexia. She was initially diagnosed with appendicitis based on physical examination and abdominal computed tomography scan and was sent to the operating room for surgical exploration. The definite diagnosis of the patient was acute ovarian torsion complicated with cystic teratoma. Primary clinicians in the ED should pay more attention to acute ovarian torsion in young children because it is difficult to diagnose in time to salvage the gynecological function when the clinical presentations masquerade as perforated appendicitis.

Clinical efficacy of house dust mite-specific immunotherapy in asthmatic children.

BACKGROUND: Immunotherapy has been widely used in the treatment of allergic diseases. We evaluated the clinical efficacy of specific immunotherapy with extracts of Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df) in children with asthma. METHODS: All 40 children had moderate-to-severe asthma and positive allergen tests for Dp and Df. All required daily medication. They were randomly assigned to two groups: Half of them received immunotherapy with subcutaneous injections of Dp and Df extracts, while the other half were not given immunotherapy. Participants were followed up for more than 6 months. RESULTS: Children in both groups had apparent improvements in medication use and symptoms after 6 months. The mean medication scores declined from 3.6 +/- 1.14 to 1.7 +/- 0.66 in the immunotherapy group (p < 0.01) and from 3.35 +/- 0.87 to 2.4 +/- 1.09 in the control group (p < 0.01). There was a significant difference between the two groups (mean difference 0.95; p < 0.01). The symptom score improved in the immunotherapy group from 2.65 +/- 0.98 to 1.20 +/- 1.00 (p < 0.01) and in the control group from 2.55 +/- 0.99 to 1.40 +/- 0.88 (p < 0.01), with a significant difference between the two groups (mean difference 0.3; p < 0.01). The number of office visits in the immunotherapy group was greater than that of the controls, but the frequencies of emergency room visits and hospitalization decreased. CONCLUSION: Our study showed that specific immunotherapy with Dp and Df was beneficial for asthmatic children.

Soluble interleukin-10 and transforming growth factor-beta in children with acute exacerbation of allergic asthma.

Cytokine-mediated interactions among inflammatory cells may contribute to pathogenesis of allergic asthma. To understand the role of soluble interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) on the disease activity and regulation in asthma, changes in serum concentrations of IL-10 and TGF-beta elaborated by activated T-lymphocyte before and after prednisolone therapy with clinical improvement were determined. Circulating levels of IL-10 and TGF-beta in sera from 16 normal control subjects and in sera from 22 allergic asthmatic children with acute exacerbation and in stable condition were respectively detected by commercially available enzyme-linked immunosorbent assay kits. The mean concentrations of serum IL-10 in asthmatics with acute exacerbation (6.77 +/- 4.08 pg/mL) and during stable condition (5.14 +/- 1.17 pg/mL) were lower than that in control subjects (7.15 +/- 4.72 pg/mL). However, the difference was not statistically significant among these three study groups. The mean concentration of serum TGF-beta in stable asthmatics (40.73 +/- 15.95 pg/mL) was significantly higher than that in asthmatics with acute exacerbation (27.64 +/- 3.66 pg/mL; p < 0.05) and that in healthy control group (28.77 +/- 8.35 pg/mL; p < 0.05), while there was no statistical difference between the latter two groups. This study provides further evidence that serum TGF-beta, rather than IL-10, may play a role in regulation of disease activity and serve as an indicator for clinical control of allergic asthmatics.

Montelukast as monotherapy in children with mild persistent asthma.

The cysteinyl leukotrienes cause bronchoconstriction, increased mucus production and airway inflammation, three major features of asthma. Several randomized controlled trials have shown the efficacy of leukotriene receptor antagonists for improving asthma outcomes. The drug is favored for treating childhood asthma, where poor compliance with inhalation therapy is a therapeutic challenge. To assess the effectiveness of Montelukast in asthmatic children under real-life conditions, a prospective, single-arm, multicenter, open-label observational study was performed on asthmatic children 2- to 14-years-old with a history of physician-diagnosed mild persistent asthma. Montelukast was given once daily for 12 consecutive weeks. By the end a significant improvement of the daytime asthma symptom score, nighttime asthma score, peak expiratory flow rate (PEFR) and mean score of the investigators' global evaluation was noted (p < 0.05). These results suggest that montelukast is an effective monotherapy controller in children with mild persistent asthma.