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The association between air pollution, allergic rhinitis (AR), and obesity has not been studied. From 2007 to 2011, 52 obese and 152 non-obese children (7–17 years old) with AR were recruited. Pediatric-Rhinoconjunctivitis-Quality-of-Life Questionnaire (PRQLQ) and nasal peak expiratory flow (NPEF) were tested. Association between the scores and rates of the two tests and mean air pollutant concentrations within 7 days before the tests were compared. When exposed to higher concentrations of CO, PM10, and PM2.5, the rates of worse nasal discomfort were 39.4%, 44.4% and 39.3% in obese children; and 18.0%, 21.9% and 19.7% in non-obese children, respectively. Compare to non-obese children, the rates in obese children were higher for CO (odds ratio (OR) 3.54, 95% confidence interval (CI) 1.15 ~ 10.92); PM10 (OR 3.26, 95% CI 1.01 ~ 10.57) and PM2.5 (OR 3.30; 95% CI 1.03 ~ 10.54). In obese children, correlations between higher concentrations of CO, PM10, PM2.5 and higher nasal discomfort (higher PRQLQ); and correlations between higher concentrations of CO, PM10, PM2.5, NMHC (non-methane hydrocarbon) and higher nasal mucosa inflammation (lower NPEF) were noted. Obesity negatively affected AR severity when AR children experienced higher concentrations of CO, PM10, and PM2.5. Increased nasal inflammation induced by air pollutants might be the underlying mechanism.

Herpes zoster is a relatively rare infectious disease in the pediatric population, as compared with adults, which is due to the reactivation of latent Varicella−Zoster virus. We report a 7-year-old child without any history of varicella, who first experienced skin pain and later presented skin lesions in dermatomal distribution. Finally, the patient was diagnosed with herpes zoster. We aim to emphasize that herpes zoster could occur in immunocompetent children and may be due to the reactivation of the vaccine strain or previous subclinical infection.

Background: Asthma animal models provide valuable information about the pathogenesis and the treatment of asthma. An ovalbumin (OVA)/complete Freund’s adjuvant (CFA)-sensitized model was developed to induce neutrophil-dominant asthma and to investigate whether fungal immunomodulatory peptide-fve (FIP-fve) could improve asthma features in the OVA/CFA-sensitized model. Methods: We used female BALB/c mice and sensitized them intraperitoneally with OVA/CFA on days 1, 2, and 3. On days 14, 17, 21, 24, and 27, they were challenged with intranasal OVA. The airway hyper-responsiveness (AHR) was detected by BUXCO, inflammatory cells were stained with Liu’s stain, the cytokines were detected using ELISA, and the airway inflammation was analyzed with hematoxylin and eosin stain. Results: According to the results, OVA/CFA sensitization could induce AHR, high levels of IgE, and inflammatory cells especially neutrophils infiltration in the lung and airway inflammation. IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, IL-25, IL-33, and transforming growth factor-β (TGF-β) increased in the OVA/CFA-sensitized mice. OVA/CFA-sensitized mice treated with FIP-fve not only increased IL-12 and IFN-γ but also decreased IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-25, IL-33, and TGF-β in the bronchoalveolar lavage fluid. Moreover, FIP-fve significantly decreased neutrophil infiltration in the lung. Conclusion: The OVA/CFA model induced neutrophilic asthma successfully, and FIP-fve improved neutrophil-dominant asthma.

Background: Sensitization to allergen has long been known to be relate to childhood allergic diseases. Polysensitised children have more severe atopic diseases, whereas allergic rhinitis or asthma children with cosensitized to food and inhalant allergens were under-researched. Objective: To realize the association between sensitization to food allergens and pediatric allergic rhinitis and asthma in Taiwan. Methods: We included 138 participants with sensitized to allergen as assessed by serum-specific IgE. 87 of 138 participants had allergic rhinitis and 51 participants had asthma. All participants underwent a physical examination and measurement of serum total and specific IgE values. Besides, nasal peak expiratory flow rate (nPEFR) that was performed by the participants with allergic rhinitis and were requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQ). Lung function test and asthma control test (ACT)/child asthma control test (C-ACT) were performed by the participants with asthma. Results: 39 of 87 allergic rhinitis participants with sensitized to food and inhalant allergens (AR food group), 48 of 87 allergic rhinitis participants with sensitized to inhalant allergen alone (AR inhalant group). The AR food group had significantly lower nPEFR values and higher total IgE values (p

Background: Enterovirus-D68 (EV-D68) has been endemic in Taiwan for some years with a small number of positive cases. Detailed information about respiratory presentation is lacking. This study characterized the clinical course in children admitted to the medical center and regional hospital in Taichung during 2015. Methods: Retrospective chart review of patients with confirmed EV-D68 infection admitted to the medical center and regional hospital in Taichung with respiratory symptoms in the second half of 2015. Past medical history, clinical presentation, management, and course in hospital were collected and analyzed. Simple demographic data and clinical symptoms were also collected from patients confirmed with EV-D68 infection who visited clinics in Taichung. Results: Six children were included. Two patients had a prior history of asthma or recurrent dyspnea, and one had other preexisting medical comorbidities. One child was admitted to the pediatric intensive care unit. All the patients were cured. Cough, rhinorrhea, tachypnea and fever were the most common clinical symptoms among inpatients, while influenza-like illness (ILI) was prevalent in outpatients. Conclusion: EV-D68 infection resulted in respiratory presentations of asthma-like illness in the hospitalized pediatric population. Patients with a prior history of asthma or recurrent dyspnea appear to be more severely affected. Key Words: enterovirus D68, respiratory presentation, taiwan

House dust mites (HDMs) are one of the most important allergy-causing agents of asthma. In central Taiwan, the prevalence of sensitization to

Background Allergic asthma, a chronic airway inflammatory disease, is a critical public health problem. Indoor house dust mites (HDMs) could cause allergic asthma. The prevalence of sensitization to Dermatophagoides microceras (Der m) was approximately 80% and is related to the immunoglobulin E crossing-reactivity of mites belonging to the same genus, Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farina (Der f). However, studies on Der m are scant. Methods We used integrated OMICs approaches to identify and characterize the group 2 mite allergen-like protein in Der m (Der m 2). We established a Der m 2-induced allergic asthma mouse model and treated the mice with a fungal immunomodulatory protein (FIP-fve) isolated from Flammulina veluptipes to evaluate the allergenicity of Der m 2 and the immunomodulatory effects of FIP-fve. Results By performing de novo draft genome assembly and comparative genome analysis, we identified the putative 144-amino acid Der m 2 in silico and further confirmed its existence through liquid chromatography–tandem mass spectrometry. Der m 2 is a lipopolysaccharides (LPS)-binding protein. Thus, we examined the LPS-binding activity of recombinant Der m 2 by performing molecular docking analysis, co-immunoprecipitation (Co-IP), and a pull-down assay. Der m 2 elicited the production of pro-inflammatory cytokines, interleukin (IL)-6, and IL-8 in BEAS-2B cells, a human bronchial epithelial cell line, and induced airway hyperresponsiveness in mice. Furthermore, in mice sensitized with Der m 2, the administration of FIP-fve in either the earlier stage or the late stage, FIP-fve alleviated allergic asthma by moderating airway inflammation and remodeling. Conclusions Der m 2 induced inflammatory responses in cell and mouse models. FIP-fve alleviated inflammation in Der m 2-induced asthma in mice by exerting an immunomodulatory effect.

Background Studies have confirmed the detrimental effects of air pollutants on allergic disease patients. However, individuals who are most vulnerable have not been completely identified. Methods Clinical study: During 2007 to 2011, 225 children aged 6 to 15 years with allergic rhinitis (AR) were recruited from a hospital in Taichung City, Taiwan. They were classified based on sensitivity to house dust mites, such as Dermatophagoides pteronyssinus, Blomia tropicalis (Bt), or Dermatophagoides microceras. Correlations between Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) scores, allergen-specific immunoglobulin E levels, and air pollution levels were evaluated. Epidemiological study: Records of 9868 children with AR who were matched for study years, age, and city of the clinical study were obtained from a national database. Correlations between clinic visits for AR, topical AR drug prescriptions, and air pollution levels were evaluated. The air pollutants included sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), particles 10), particles 2.5), nitric oxide (NO), nitrogen dioxide (NO2), nonmethane hydrocarbon (NMHC), and methane (CH4). Results Epidemiological study: CO, NO, NO2, and CH4 levels were significantly correlated with topical AR drug prescriptions in boys. However, in girls, only CH4 level was significantly correlated. Clinical study: Positive correlations between the PRQLQ score and air pollutants were noted in boys but not in girls. After adjusting for confounders, correlations between CO, PM2.5, and NO2 levels were noted in boys sensitized to Bt but not in those sensitized to other mites. Conclusion Boys with AR were more vulnerable to air pollutants than girls. Bt-sensitized boys with AR were more vulnerable to air pollutants than girls and those sensitized to other mites.

Background/Aims: Atopic dermatitis (AD) is a common disease in infancy, for which topical steroids are the first-line therapy but have side effects. Innovative approaches are needed to reduce the burden of AD and corticosteroid usage in infants. Methods: The once-daily consumption of heat-treated probiotic Lactobacillus paracasei GM-080 or placebo for 16 weeks as supplementary approach to topical treatment with fluticasone propionate cream was compared in AD infants aged 4–30 months. Outcomes were SCORAD and its subscores, TEWL, Infants’ Dermatitis Quality of Life Index (IDQOL), corticoid “sparing effect,” CCL17/TARC, and IgE status. Results: SCORAD, objective SCORAD, itching, and IDQOL decreased significantly (p < 0.001) over the treatment period in both treatment groups. Slight decreases (ns) were noted in TEWL in lesional and unaffected skin and CCL17 levels. There were no differences between the treatment groups. Total IgE increased over the treatment period in both groups, with significantly higher increase in the heat-treated probiotic group (p = 0.038). There was no evidence of a corticoid “sparing effect” by the probiotic. Conclusions: In this design, the probiotic L. paracasei was not beneficial as a complementary approach to topical corticosteroids in infants with AD. However, slight beneficial effects may have been masked by the moderate potency corticoid.

Asthma animal models provide valuable information about the pathogenesis and the treatment of asthma. An ovalbumin (OVA)/complete Freund's adjuvant (CFA)-sensitized model was developed to induce neutrophil-dominant asthma and to investigate whether fungal immunomodulatory peptide-fve (FIP-fve) could improve asthma features in the OVA/CFA-sensitized model.We used female BALB/c mice and sensitized them intraperitoneally with OVA/CFA on days 1, 2, and 3. On days 14, 17, 21, 24, and 27, they were challenged with intranasal OVA. The airway hyper-responsiveness (AHR) was detected by BUXCO, inflammatory cells were stained with Liu's stain, the cytokines were detected using ELISA, and the airway inflammation was analyzed with hematoxylin and eosin stain.According to the results, OVA/CFA sensitization could induce AHR, high levels of IgE, and inflammatory cells especially neutrophils infiltration in the lung and airway inflammation. IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, IL-25, IL-33, and transforming growth factor-β (TGF-β) increased in the OVA/CFA-sensitized mice. OVA/CFA-sensitized mice treated with FIP-fve not only increased IL-12 and IFN-γ but also decreased IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-25, IL-33, and TGF-β in the bronchoalveolar lavage fluid. Moreover, FIP-fve significantly decreased neutrophil infiltration in the lung.The OVA/CFA model induced neutrophilic asthma successfully, and FIP-fve improved neutrophil-dominant asthma.

Additional file 1: Appendix 1. Individual application project and date description (University Selection Admission Committee). Appendix 2. Timeline for assessment and distribution (University Entrance Examination Center). Appendix 3. Time-series data for page views for both departments in pre- (February 26–March 22, 2018) and post-PA (March 23–May 17, 2018) periods.

House dust mites (HDMs) are one of the most important allergy-causing agents of asthma. In central Taiwan, the prevalence of sensitization to Dermatophagoides microceras (Der m), a particular mite species of HDMs, is approximately 80% and is related to the IgE crossing reactivity of Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). Integrated OMICs examination was used to identify and characterize the specific group 1 mite-allergic component (Der m 1). De novo draft genomic assembly and comparative genome analysis predicted that the full-length Der m 1 allergen gene is 321 amino acids in silico. Proteomics verified this result, and its recombinant protein production implicated the cysteine protease and α chain of fibrinogen proteolytic activity. In the sensitized mice, pathophysiological features and increased neutrophils accumulation were evident in the lung tissues and BALF with the combination of Der m 1 and 2 inhalation, respectively. Principal component analysis (PCA) of mice cytokines revealed that the cytokine profiles of the allergen-sensitized mice model with combined Der m 1 and 2 were similar to those with Der m 2 alone but differed from those with Der m 1 alone. Regarding the possible sensitizing roles of Der m 1 in the cells, the fibrinogen cleavage products (FCPs) derived from combined Der m 1 and Der m 2 induced the expression of pro-inflammatory cytokines IL-6 and IL-8 in human bronchial epithelium cells. Der m 1 biologically functions as a cysteine protease and contributes to the α chain of fibrinogen digestion in vitro. The combination of Der m 1 and 2 could induce similar cytokines expression patterns to Der m 2 in mice, and the FCPs derived from Der m 1 has a synergistic effect with Der m 2 to induce the expression of pro-inflammatory cytokines in human bronchial epithelium cells.

Objective: The main objective of this study was to evaluate the efficacy and safety of Lactobacillus rhamnosus in children aged 4–48 months with atopic dermatitis. Methods: The design of this study was a two-center, double-blind, randomized, and placebo-controlled study with two parallel groups to evaluate the efficacy and safety profile of L. rhamnosus in children aged 4–48 months with atopic dermatitis diagnosed using Hanifin and Rajka criteria and with a Scoring of Atopic Dermatitis (SCORAD) ≥ 15 at enrollment. The duration of this study was 8 weeks with a total of five visits. The enrolled patients were allocated into either a treatment group (one ComProbi capsule containing L. rhamnosus a day) or a control group (one capsule of placebo a day) at a ratio of 1:1. The primary endpoint was to compare the mean change from baseline in SCORAD after 8 weeks of treatment. The other secondary end points were to compare the following: the mean changes from baseline in SCORAD at postbaseline visits, the frequency and total amount of the use of corticosteroids during the 8-week treatment, the frequency of atopic dermatitis and the symptom-free duration, the mean changes from baseline in Infant Dermatitis Quality of Life Questionnaire at Week 4 and Week 8, and the mean changes from baseline in the Dermatitis Family Impact Questionnaire at Week 4 and Week 8. Results: The mean changes in SCORAD from baseline at Week 8 was −21.69 ± 16.56 in the L. rhamnosus group and −12.35 ± 12.82 in the placebo group for the intent-to-treat population (p = 0.014). For the per-protocol population, the mean change of SCORAD from baseline was −23.20 ± 15.24 in the L. rhamnosus group and −12.35 ± 12.82 in the placebo group (p = 0.003). Significant differences were demonstrated between groups at Week 8 in intensity in the intent-to-treat population and per-protocol population. Throughout the period, the amount of topical corticosteroids used showed no difference between groups. No significant difference was noted in the overall symptom-free durations compared with the placebo group. Infant Dermatitis Quality of Life Questionnaires and Dermatitis Family Impact Questionnaires scores improved significantly at Week 4 and Week 8 but did not reach statistical significance. Adverse events were documented in 14/33 patients in the L. rhamnosus group (42.42%, 35 events) and in 15/33 placebo patients (45.45%, 37 events). Conclusions: The results of this study indicated that L. rhamnosus was effective in decreasing symptoms of atopic dermatitis after an 8-week treatment by comparing the mean change of SCORAD from baseline with a placebo (p

Novel ADCC effector cells expressing the V-variant or F-variant of FcγRIIIa (CD16a) and firefly luciferase under the control of a chimeric promoter incorporating recognition sequences for the principal transcription factors involved in FcγRIIIa signal transduction, together with novel target cells overexpressing a constant high level of the specific antigen recognized by rituximab, trastuzumab, cetuximab, infliximab, adalimumab, or etanercept, confer improved sensitivity, specificity, and dynamic range in an ADCC assay relative to effector cells expressing a NFAT-regulated reporter gene and wild-type target cells. The effector cells also contain a normalization gene rendering ADCC assays independent of cell number or serum matrix effects. The novel effector and target cells in a frozen thaw-and-use format exhibit low vial-to-vial and lot-to-lot variation in their performance characteristics reflected by CVs of 10% or less. Homologous control target cells in which the specific target gene has been invalidated by genome editing providing an ideal control and a means of correcting for nonspecific effects were observed with certain samples of human serum. The novel effector cells and target cells expressing noncleavable membrane-bound TNFα have been used to quantify ADCC activity in serum from patients with Crohn’s disease treated with infliximab and to relate ADCC activity to drug levels.

To evaluate whether arthroscopic lateral retinacular release and the modified Elmslie–Trillat operation improve osteoarthritis (OA) progression and clinical outcomes in patients with severe isolated lateral patello-femoral OA. Nine women (11 knees) and one man (one knee) with isolated late-stage lateral patello-femoral OA underwent surgery. The severity of patello-femoral OA was recorded using the Merchant method, while the level of pain and anterior knee function were scored using the visual analogue scale (VAS) and Kujala knee scores, respectively. The articular cartilage was graded under arthroscopy using the Outerbridge classification. All of the patients underwent the modified Elmslie–Trillat operation after arthroscopic surgery, including lateral retinacular release. Ten patients (12 knees) had a mean 6.45 ± 0.80 mm of medial transfer, 6.02 ± 0.80 mm of anterior transfer of the tibial tubercle, and follow-up of 67.0 months. The mean VAS and Kujala knee scores improved from 8 ± 0.17 preoperatively to 2.33 ± 0.33 on the last follow-up and from 43.08 ± 2.09 to 68.83 ± 2.59, respectively (both p

Atopic dermatitis (AD) is a common disease in infancy, for which topical steroids are the first-line therapy but have side effects. Innovative approaches are needed to reduce the burden of AD and corticosteroid usage in infants.The once-daily consumption of heat-treated probiotic Lactobacillus paracasei GM-080 or placebo for 16 weeks as supplementary approach to topical treatment with fluticasone propionate cream was compared in AD infants aged 4-30 months. Outcomes were SCORAD and its subscores, TEWL, Infants' Dermatitis Quality of Life Index (IDQOL), corticoid "sparing effect," CCL17/TARC, and IgE status.SCORAD, objective SCORAD, itching, and IDQOL decreased significantly (p0.001) over the treatment period in both treatment groups. Slight decreases (ns) were noted in TEWL in lesional and unaffected skin and CCL17 levels. There were no differences between the treatment groups. Total IgE increased over the treatment period in both groups, with significantly higher increase in the heat-treated probiotic group (p = 0.038). There was no evidence of a corticoid "sparing effect" by the probiotic.In this design, the probiotic L. paracasei was not beneficial as a complementary approach to topical corticosteroids in infants with AD. However, slight beneficial effects may have been masked by the moderate potency corticoid.

Steroid-insensitive asthma-related airway inflammation is associated with the expression of epidermal growth factor receptor (EGFR) tyrosine kinase in asthmatic bronchial epithelium. Proinflammatory cytokines IL-6 and IL-8 are related to steroid-insensitive asthma. It is currently unknown how EGFR-tyrosine kinase inhibitors (EGFR-TKIs) affects house dust mite (HDM)-induced asthma in terms of inflammatory cytokines related to steroid-resistant asthma and further signaling pathway. Cytokine expressions and EGFR signaling pathway were performed by ELISA, reverse transcriptase PCR, real-time PCR, and Western blot in cell-line models. AMP-activated protein kinase (AMPK) pathway-related inhibitors were applied to confirm the association between EGFR-TKI and AMPK pathway. HDM induced IL-6 and IL-8 in a dose-dependent manner. Both Erlotinib (Tarceva) and Osimertinib (AZD-9291) reduced the levels of HDM-stimulated IL-6 and IL-8 levels in BEAS-2B cells. AZD-9291 was more effective than Erlotinib in inhibiting phospho-EGFR, and downstream phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and phopho-signal transducer and activator of transcription 3 (p-STAT3) pathway signaling. In addition, AMPK pathway-related inhibitor, Calcium-/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, down-regulated IL-8, but EGFR-TKI had no effect on AMPK pathway. Our findings highlight EGFR-TKIs, Tarceva, and AZD-9291, attenuate HDM-induced inflammatory IL-6 and IL-8 cytokines via EGFR signaling axis pathway, but not AMPK signaling pathway.

Flavanones demonstrate a propensity to antiproliferation and induce apoptosis of malignant cells. Among the 4 flavanones under study, 2'-hydroxyflavanone exhibited the greatest potency to reduce the cell viability of 143 B cells in 4 osteosarcoma cells. Flow cytometry analysis showed that 2'-hydroxyflavanone increased the hypodiploid cells in the sub-G1 phase but resulted in the reduced DNA content in the G0/G1 phase in 143 B cells. The 2'-hydroxyflavanone-induced apoptosis in 143 B cells was confirmed by 4'-6-diamidino-2-phenylindole staining and mitochondrial membrane potential (Δψm) assay. Increasing expressions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor 5 (DR5) were found in 2'-hydroxyflavanone-treated cells. Moreover, 2'-hydroxyflavanone increased the expressions of B-cell lymphoma-extra small, cytochrome c, and cleavage poly (ADP-ribose) polymerase but downregulated B-cell lymphoma/leukemia-2expressions in 143 B cells. Furthermore, in vivo experiments showed that 2'-hydroxyflavanone inhibited the tumor growth of 143 B cells. 2'-hydroxyflavanone induced the apoptosis of 143 B cells via the extrinsic TRAIL- and intrinsic mitochondrial-dependent pathways, indicating its potential for inducing cancer apoptosis in osteosarcoma.

Renal manifestations of tuberous sclerosis complex (TSC) occur with a high frequency and a wide range of severity. The onset and complications of each affected organ depend on the age. This study aimed to investigate the associations between comorbidities, frequency, and size of cysts/angiomyolipomas of TSC and the patients in the different ages.We performed a systematic evaluation of patients with TSC at integrated clinics for TSC. The patients were diagnosed with TSC according to Roach's clinical diagnostic criteria. All the patients underwent a systematic evaluation with a medical history review, recording of cutaneous manifestations, magnetic resonance imaging of the brain, chest computed tomography scan, and cardiac echography. Each patient was routinely evaluated with renal magnetic resonance imaging.Of the 57 patients with TSC, renal lesions or manifestations were observed in 38.5 % at preschool-age group (6 years) that increased to 75.0, 85.7, and 100 % in school-age group (6-18 years), young adulthood group (18-30 years), and middle-aged group30 years, respectively. Renal complications or interventions were found in 72.7 % of patients30 years. There was a strongly positive association between the size of renal lesions and age (p0.001). Comorbidities of TSC were significantly correlated with pulmonary lymphangiomyomatosis (p0.001) and seizure remission (p = 0.018).The results indicate a positive association of progressively growing renal lesions in patients with TSC with increasing age. It is mandatory for clinicians that monitor the high-risk patients to minimize and prevent renal complications in the future.

BackgroundNasal irrigation has been used as adjunctive therapy for sinonasal disease but is under-researched in children. The study aim was to evaluate the effectiveness of nasal irrigation with normal saline in the management of acute sinusitis in atopic children.MethodsWe enrolled 60 atopic children with acute sinusitis, of whom 29 received nasal irrigation with normal saline and 31 did not receive nasal irrigation. All participants underwent a nasal peak expiratory flow rate (nPEFR) test, a nasal smear examination, and radiography (Water's projection) and were requested to complete a Pediatric Rhinoconjunctivitis Quality-of-Life Questionnaire (PRQLQ) during the baseline visit. All participants were requested to record symptoms in a daily diary and were followed up at 1-week intervals. A physical examination, nasal smear, and nPEFR were performed at each visit, and all daily diaries were collected. At the final visit (after 3 weeks), the symptom diaries were reviewed and participants were requested to complete the PRQLQ again. nPEFR, radiography, and a nasal smear were also repeated.ResultsThere were significant improvements in mean PRQLQ and nPEFR values (p 0.05). The irrigation group recorded significant improvements in eye congestion, rhinorrhea, nasal itching, sneezing, and cough symptoms compared with the non-irrigation group.ConclusionNasal irrigation is an effective adjunctive treatment for acute sinusitis in atopic children.

Antibiotics during infancy, delivery, and breastfeeding affect the intestinal microbiota in early life and is associated with allergic disease. Gastroenteritis (GE) during infancy also affects intestinal microbiota in early life, however, its relationship to allergic disease has not been investigated. Data of 45,499 males and 49,430 females, from birth to 5 years of age, were collected from a national database in Taiwan. Subjects were categorized into early GE (GE within 0–6 months) and non-early GE group (no GE within 0–6 months). The rates of asthma (AS), allergic rhinitis (AR), and atopic dermatitis (AD) over 5 years were evaluated and compared between the groups. In patients with AS, AR, and AD, the number of clinical visits and drug prescriptions for the allergic disease was also evaluated to assess the effect of early GE on allergic disease. After adjusting for the effect of GE in later life and other factors, the rates of AS [OR (odds ratio) 1.54, 95% confidence interval (CI) 1.48–1.60], AR [OR 1.49, 95% CI 1.45–1.54], and AD [OR 1.40, 95% CI 1.33–1.47] were higher in the early GE group than in the non-early GE group. The magnitude of the increase was higher in females than in males. In those with AS, AR, and AD, the number of clinical visits and drug prescriptions was not different between the early GE and non-early GE groups. In children with early GE, good control of GE in the following years lowered the rate of allergic disease. Early-life GE was associated with increased rates of AS, AR, and AD in later life and this was trend more prominent in females.

Since 1998 in Taiwan, enterovirus (EV) 71 epidemics have caused encephalomyelitis and placed a significant burden on parents and physicians. In this study, we present clinical manifestations, magnetic resonance (MR) imaging findings, and neurological sequelae on epidemic EV-infected patients with encephalomyelitis. Of the 46 patients, 14 patients presented with neurological sequelae; of them, 3 patients suffered from complications of mental regression. Predictors of unfavorable neurological sequelae were myoclonic jerks (> 4 times/night) and pleocytosis (167/μL) of the cerebrospinal fluid (CSF). Results from viral culture and MR imaging indicated that positive identification of EV71 infection was associated significantly with lesions on MR imaging. Our results show that hand-foot-mouth disease carries a higher risk of encephalomyelitis and that frequent myoclonic jerks and pleocytosis of the CSF are risk factors for subsequent neurological sequelae. Positive identification of EV71 might be useful as a predictor of lesions in MR imaging.

Background Environmental tobacco smoke (ETS) is a risk factor for asthma. Importantly, cigarette smoke can decrease the adherence of epithelial cells and increase detachment. The adhesion molecule E-cadherin (CDH1) has an essential role in the formation of epithelial junction. Turnover of the extracellular matrix, which is characterized by airway remodeling, depends on the imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs). Objective To evaluate the effects of ETS exposure and CDH1, MMP-3, and TIMP-1 genetic polymorphisms on childhood asthma. Methods The CDH1 C-160A, MMP-3 −1171, and TIMP-1 T372C genotypes were identified by polymerase chain reaction in 299 asthmatic children and 383 healthy controls. Results More ETS exposure (>5 vs 0 cigarettes/day; odds ratio [OR], 1.45; 95% confidence interval [CI], 1.05–2.01) and the presence of CDH1 AA/CA genotypes (OR, 1.53; 95% CI, 1.08–2.17) were associated with childhood asthma. Compared with children with less ETS exposure (0–5 cigarettes/day) and the CDH1 CC genotype, those with less ETS exposure and the CDH1 AA/CA genotypes and those with more ETS exposure and the CDH1 CC genotype had a moderate risk of asthma. The greatest risk for asthma was in children with more ETS exposure and the CDH1 AA/CA genotypes (OR, 3.03; 95% CI, 1.81–5.06), and this interaction between CDH1 polymorphism and ETS exposure was significant. In addition, asthma cases with more ETS exposure or the CDH1 AA/CA genotypes had obviously increased eosinophil counts. Conclusion Susceptible CDH1 genotypes might modulate the development of asthma, especially for children exposed to ETS.

Purpose Both atopic diseases (AD) and attention-deficit/hyperactivity disorders (ADHD) are common pediatric disorders that may lead to mental and physical complications. This population-based, case-control design is to correlate the risk of ADHD with AD among a pediatric population. Methods By using a Longitudinal Health Insurance Database ranged from 2002 to 2009, 4692 children with ADHD and 18,768 randomly selected controls were enrolled. Odds ratios (OR) of ADHD were calculated for the association with AD. Results The children with ADHD had a higher rate of AD than controls, particularly allergic rhinitis and allergic conjunctivitis. The corresponding ORs were 1.81 (95% confidence interval [CI], 1.69–1.93) and 1.69 (95% CI, 1.58–1.81), respectively. Despite the lower prevalence, children with atopic dermatitis and asthma were also at higher risk of ADHD, with ORs of 1.80 (95% CI, 1.58–2.05) and 1.48 (95% CI, 1.24–1.78). Logistic regression analysis estimated ORs showed ADHD risk was higher for those living in urban areas. The risk of ADHD increased with numbers of AD and age. Conclusions Most of the children with ADHD had a strong association with AD, especially allergic rhinitis. Awareness of these comorbidities may help clinicians to provide better comprehensive management and reduce the burden of disease.

This study aimed to examine the ability of acute (99m)Tc DMSA scan for predicting dilating (grades III-V) vesicoureteral reflux (VUR) after a first febrile urinary tract infection in children aged 2 years or younger.All children underwent ultrasonography (US), (99m)Tc DMSA scan, and voiding cystourethrography. Sensitivity, specificity, positive and negative predictive values, likelihood ratios, and receiver operating characteristic curves were performed to assess the diagnostic accuracy for predicting dilating VUR. Follow-up scan was performed at least 6 months after the acute infection to evaluate the presence of renal scarring (RS) or new scars.Of the 473 children analyzed (289 boys and 184 girls; median age, 5 months), 282 (59.6%) had abnormal acute (99m)Tc DMSA scan findings. There was VUR in 153 children (32.3%), whereas 95 (20.1%) had dilating VUR. The sensitivity and negative predictive value in predicting dilating VUR were 95.8% and 97.9%, respectively, for (99m)Tc DMSA and 97.9% and 98.6%, respectively, for combined US and (99m)Tc DMSA, whereas the positive and negative likelihood ratios were 1.90 and 0.08, respectively, for (99m)Tc DMSA and 1.57 and 0.06, respectively, for combined studies. On multivariate analysis, dilating VUR was a predictor for developing RS and new scars.Our results reveal the usefulness of acute (99m)Tc DMSA scan for predicting dilating VUR in children with a first febrile urinary tract infection. A voiding cystourethrography is indicated in only children with abnormalities found on a (99m)Tc DMSA and/or a US. The presence of dilating VUR predisposes to developing RS and new scars.

BACKGROUND AND PURPOSE Autophagic cell death is considered a self-destructive process that results from large amounts of autophagic flux. In our previous study, GMI, a recombinant fungal immunomodulatory protein cloned from Ganoderma microsporum, induced autophagic cell death in lung cancer cells. The aim of this study was to examine the role of autophagosome accumulation in GMI-mediated cell death. EXPERIMENTAL APPROACH Western blot analysis, flow cytometry and confocal microscopy were used to evaluate the effects of different treatments, including silencing of ATP6V0A1 by use of short hairpin RNAi, on GMI-mediated cell death, lung cancer cell viability and autophagosome accumulation in vitro. KEY RESULTS Lysosome inhibitors bafilomycin-A1 and chloroquine increased GMI-mediated autophagic cell death. GMI and bafilomycin-A1 co-treatment induced the accumulation of large amounts of autophagosomes, but did not significantly induce apoptosis. GMI elicited autophagy through the PKB (Akt)/mammalian target of rapamycin signalling pathway. Silencing of ATP6V0A1, one subunit of vesicular H+-ATPases (V-ATPases) that mediates lysosome acidification, spontaneously induced autophagosome accumulation, but did not affect lysosome acidity. GMI-mediated autophagosome accumulation and cytotoxicity was increased in shATP6V0A1 lung cancer cells. Furthermore, ATP6V0A1 silencing decreased autophagosome and lysosome fusion in GMI-treated CaLu-1/GFP-LC3 lung cancer cells. CONCLUSION AND IMPLICATIONS We demonstrated that autophagosome accumulation induces autophagic cell death in a GMI treatment model, and ATP6V0A1 plays an important role in mediating autophagosome-lysosome fusion. Our findings provide new insights into the mechanisms involved in the induction of autophagic cell death.

Background: The association between neonatal jaundice and childhood asthma is a new finding of two reports. The purpose of the study was to verify their results. Methods: Data from 11,321 children were collected from the National Health Insurance Research Database. Their claims data were evaluated from birth to 10 yr old. Children were analyzed as case (those with neonatal jaundice) and controls (those without neonatal jaundice). The diagnostic criteria for asthma were as follows: at least four asthma diagnoses at outpatient services and emergency department (ED), or one asthma diagnosis during an admission. In children fitting the asthma criteria, those with no asthma diagnosis after 1 yr of age were excluded. Mantel–Haenszel’s odds ratios were calculated after adjustment for the following confounders: preterm/low birth weight, neonatal infection, other respiratory conditions, other birth conditions, and gender. Asthma rate, onset time, the use of drugs, upper respiratory infection and lower respiratory infection (LRI) rates, hospital admission/ED visit rates, and the effect of phototherapy were evaluated. Results: After adjustment for the confounding factors, the rate of asthma was higher in icteric children (OR: 1.64, 95% CI 1.36–1.98, p

Background Cysteinyl leukotrienes (CysLTs) play a major role in the pathogenic changes of airway inflammation in asthma treatment. The matrix metalloproteinase (MMP) family, especially MMP-9 and MMP-2 levels, can reflect the status of airway remodeling. This study was undertaken to determine the role of a specific CysLT receptor antagonist in inhibition of airway inflammation and reversal of airway remodeling. Methods Ovalbumin (OVA)-sensitized BALB/c mice were fed with a specific leukotriene receptor antagonist (MK-679), prednisolone or placebo from Days 15 to 27. Airway hyperreactivity, bronchoalveolar lavage fluid (BALF), and sera were analyzed. Pulmonary histology was obtained, and the levels of MMP-2 and MMP-9 in BALF were measured. Results The OVA-sensitized mice developed significant airway inflammatory responses, including extensive eosinophils trafficking into BALF and lung interstitium, goblet cell hyperplasia, mucus hypersecretion, elevated serum immunoglobulin (Ig) E, and decreased level of serum IgG2a. Administration of MK-679 could reduce airway inflammation but was not as effective as prednisolone. However, MK-679 was more effective than prednisolone for reversing subepithelial fibrotic and myofibrotic reactions of airway remodeling. The levels of MMP-2 and -9 in BALF were proportional to the extent of airway remodeling, which can reflect the effects of treatment. Both prednisolone and MK-679 reverse airway hyperresponsiveness induced by OVA-sensitized mice. Conclusion Cysteinyl leukotriene receptor plays a more important role than CysLT in the pathogenesis of allergic airway inflammation. MMP-2 and -9 may be more sensitive indicators of airway remodeling.

Background/Purpose Data on hospital admissions for children under 5 years old, concerning the admission rate, leading diagnoses, categories of disease, average hospitalization days, costs and between-year differences are scarce. Our study aims to investigate such admission profiles. Methods Five percent of admission data for children under 5 years old in 2000 and 2009 was collected from the National Health Insurance Research Database in Taiwan. We calculated the admission rate in regards to total admission, the patients' gender, the ten leading diagnoses, the ten most systemic common categories of disease, and the average hospitalization days and costs. The differences of the rates between 2000 and 2009 were evaluated by incidence rate ratios (IRR). Results The admission rate per thousand children (population) was higher in 2009 (172.9) than 2000 (153.1). The ten most common systemic categories of disease were similar in both years. Furthermore, it was observed that the hospitalization days decreased by 3.7% in 2009, while medical expenditures increased by 10.9%. Conclusions Efforts should be made to decrease the admission rate and hospitalization days in Taiwan to the levels of well-developed countries. Our data may serve as baseline data for future evaluations of child morbidity.

Background: Epidemiological research underpins the importance of effective health-care strategies for adolescents. This descriptive study compares the 10 most common diseases among Taiwanese adolescents for 2000 and 2009. Methods: Data for a total of 69 594 visits in 2000 and 65 802 visits in 2009 by adolescents aged between 10 and 20 years were collected from the National Health Insurance Research Database. A maximum of three outpatient diagnostic codes (International Classification of Disease, ninth revision) could be listed for every visit. The data categories were: principal diagnosis, patient age, and physician specialty. Results: The middle adolescent age group utilized the least amount of medical services. Respiratory (46.2% in 2000, 40.5% in 2009) and digestive (16.5% in 2000 and 16.9% in 2009) tracts were the leading two diagnostic categories for adolescent ambulatory visits. Teeth (6.8%, 6.1%) and eye (4.0%, 3.1%) problems were also among the top 10 diseases. Family practitioners, ear-nose-throat specialists, and traditional Chinese medicine physicians were the major health-care providers for Taiwanese adolescents, especially in the middle and late groups. Although noted as the first option for consultation in the early group, the role of pediatricians with regard to adolescent health care declined in importance with age. Conclusions: Nearly 99% of the population in Taiwan is covered under the national health insurance system. The different disease patterns and major health-care providers between Taiwan and other countries are compared.

Objectives Urinary tract infection (UTI) is a common bacterial infection in children that can result in permanent renal damage. This study prospectively assessed the diagnostic performance of procalcitonin (PCT) for predicting acute pyelonephritis (APN) among children with febrile UTI presenting to the paediatric emergency department (ED). Methods Children aged ≤10 years with febrile UTI admitted to hospital from the paediatric ED were prospectively studied. Blood PCT, C reactive protein (CRP) and white blood cell (WBC) count were measured in the ED. Sensitivity, specificity, predictive values, multilevel likelihood ratios, receiver operating characteristic (ROC) curve analysis and multivariate logistic regression were used to assess quantitative variables for diagnosing APN. Results The 136 enrolled patients (56 boys and 80 girls; age range 1 month to 10 years) were divided into APN (n=87) and lower UTI (n=49) groups according to 99mTc-dimercaptosuccinic acid scan results. The cut-off value for maximum diagnostic performance of PCT was 1.3 ng/ml (sensitivity 86.2%, specificity 89.8%). By multivariate regression analysis, only PCT and CRP were retained as significant predictors of APN. Comparing ROC curves, PCT had a significantly greater area under the curve than CRP, WBC count and fever for differentiating between APN and lower UTI. Conclusions PCT has better sensitivity and specificity than CRP and WBC count for distinguishing between APN and lower UTI. PCT is a valuable marker for predicting APN in children with febrile UTI. It may be considered in the initial investigation and therapeutic strategies for children presenting to the ED.

Rhinitis and sinusitis are very common medical conditions and have been shown to be frequently associated. The role of allergies in the pathogenesis of chronic rhinosinusitis has been confirmed; however, the role of allergies in acute rhinosinusitis is debatable. Nonetheless, allergies are an important factor in the development of rhinosinusitis.To evaluate the incidence of allergic rhinitis in patients with acute rhinosinusitis and identify the clinical spectrum in Taiwan.This study randomly recruited 69 participants between 3 and 12 years of age with acute rhinosinusitis over the period of one and a half years. All participants underwent a nasal peak expiratory flow rate (nPEFR) test, skin-Prick test (SPT), nasal smear examination, nasal culture, radiography (Water's projection) and were requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) as well as provide their allergic history.Among the 69 participants in the study, 27 (39.1%) participants were shown to have allergic rhinitis. The most troublesome symptoms among the 69 participants with acute rhinosinusitis were postnasal drip (3.00 ± 1.29), nasal obstruction (2.94 ± 1.39) and cough (2.67 ± 1.42). The most troublesome symptoms among the 27 participants with acute rhinosinusitis combined with allergic rhinitis were nasal obstruction (3.33 ± 1.24), postnasal drip (3.22 ± 1.09) and itchy eyes (2.74 ± 1.43) and with the higher values. In addition, the participants (≧ 6 y/o) with acute rhinosinusitis combined with allergic rhinitis had significantly lower nPEFR values compared with the nonatopic children (75.2 ± 18.2 vs 96.6 ± 21.4, p0.05). If nPEFR is below 75 mL/min, the positive predict value in the patients of acute rhinosinusitis is 75.0% combined with allergic rhinitis (sensitivity 63.2%; specificity 85.7%). Streptococcus pneumoniae (29.0%), Haemophilus influenzae (20.3%), and Moraxella catarrhalis (17.4%) were the major isolated pathogens in this study. The prevalence of colonization with Staphylococcus aureus in the 69 participants with acute rhinosinusitis was 23.2%, and 15.9% for methicillin-resistant S. aureus (MRSA).This study demonstrated that the bacteriological properties of acute rhinosinusitis among children in Taiwan are the same as those in other parts of the world; however, the prevalence of colonization by MRSA was higher than among healthy children. Second, atopic children were more likely to develop acute rhinosinusitis than nonatopic children. Third, most Taiwanese children with acute rhinosinusitis complained of postnasal drip, nasal obstruction and cough. If a child suffering from acute rhinosinusitis complained of severe nasal obstruction (nPEFR≦75 mL/min), the doctor should be alerted to atopic conditions requiring further treatment. The issues dealt with in this study may require further research with a larger sample population over an extended period of time to verify these conclusions.

The atopic march hypothesis suggests that allergy diseases often progress from atopic dermatitis to allergic asthma, and allergic rhinitis. How often can the classic progression of allergic diseases be observed in the pediatric patient population? This study aimed to observe the pattern of allergic diseases progression, onset age, disease intervals, and frequency of the allergic march. Data from the National Health Insurance Research Database in the period 1996-2008 were used to obtain a cohort of children with allergic disease. Physician's diagnosis was used to confirm the allergic disease based on the international disease coding. The age of disease onset was compared. There were 10,729 children aged

Autophagy is a self-digestive process that degrades the cytoplasmic constituents. Immunomodulatory protein, one major bioactive component of Ganoderma, has antitumor activity. In this study, recombinant fungal immunomodulatory protein, GMI, was cloned from Ganoderma microsporum and purified. We demonstrated that GMI induces lung cancer cell death by activating autophagy, but does not induce apoptotic cell death. On western blot, GMI increased LC3 conversion and decreased p53 expression in a time- and concentration-dependent manner. Cytoplasmic calcium chelator BAPTA-AM was used to prove that GMI promotes autophagy via a calcium-mediated signaling pathway. 3-methyladenine (3-MA), an autophagy inhibitor, enhanced the cytotoxicity of GMI on cell viability assay. Using VZV-G pseudotyped lentivirus-shRNA system for autophagy-related genes silencing, the capabilities of GMI to reduce cell viability and colony formation were abolished in autophagy-defective cells. Furthermore, GMI did not stimulate apoptosis after blocking of autophagy by 3-MA or shRNA knockdown system. In xenograft studies, oral administration of GMI inhibited the tumor growth and induced autophagy significantly in nude mice that had received a subcutaneous injection of A549 cells. This is the first study to reveal the novel function of GMI in activating autophagy. GMI may be a potential chemopreventive agent against non-small cell lung cancer.

Complete agenesis of the bladder and urethra is an extremely rare congenital anomaly and most of these patients are stillborn or die during infancy. We report the case of a 1-month-old female infant with bladder and urethral agenesis who presented with bilateral dilated and tortuous ectopic ureters draining into the vagina diagnosed using MR imaging. Our patient was maintained on antibiotic prophylaxis and she remained well during the 3-year follow-up. MR imaging can be used as a valuable modality for genitourinary abnormalities, particularly in cases of inconclusive ultrasound or retrograde pyelography findings.

Background To relate the expression of the matrix degrading proteinase cathepsin B and its endogenous inhibitor cystatin C in the synovial fluid (SF) to the clinical and laboratory variables of joint inflammation in gouty arthritis of the knee. Methods Thirty-nine SF samples were obtained from inflamed knees of patients with acute gout. The levels of cathepsin B, cystatin C, urokinase-type plasminogen activator (uPA), soluble uPA receptor (suPAR) and PA inhibitor type-1 (PAI-1), activities of matrix metalloproteinase-2 (MMP-2) and MMP-9, and cell counts as well as local arthritis activity scores (LAS) were examined. Results The increases of cathepsin B levels correlated with increased leukocyte and neutrophil counts, latent MMP-9 (pro-MMP-9) activities, uPA, suPAR and PAI-1 levels, and uPA/PAI-1 ratios. Increased cystatin C levels corresponded closely with increased LAS, leukocyte and neutrophil counts, pro-MMP-9 activities, uPA, suPAR and PAI-1 levels, and uPA/PAI-1 ratios. Moreover, there was a correlation between cathepsin B and cystatin C levels. Conclusions These results show a high correlation between the cathepsin B/cystatin C system and markers of joint inflammation in acute gout of the knee, demonstrating the pathologic role of cathepsin B and cystatin C in inflammation.

Background There is growing evidence of positive correlations between asthma (AS) and obesity in adults and children. Leptin is an obesity gene product secreted by white adipose tissue; elevated serum levels are found in obese adults and children. Recently, leptin has also been found to be associated with allergic rhinitis (AR). However, the links between serum leptin, atopic AS, and AR remained undetermined. Because AS and AR share common allergic inflammatory mechanisms, our aim was to determine if there were any differences in serum leptin levels between asthmatic children and nonasthmatic children with AR. Methods We studied 114 children (67 boys and 47 girls): 68 with mild intermittent-to-moderate persistent atopic AS (AS children) and 46 with mild-to-moderate persistent AR without AS (AR children; overall mean age, 8.51 years; range, 5–18 years). Body mass index (BMI), serum leptin, pulmonary function, and atopy parameters (serum IgE and eosinophil levels) were measured. Results Compared with AR children, AS children had higher body weights (kg), body mass indices (kg/cm2), and serum leptin levels (ng/mL). Multiple linear regression analyses showed that serum leptin concentrations differed significantly for girls, being overweight and between disease groups (AS and AR children). Conclusion Our results indicate that a higher serum leptin level has stronger association with mild-to-moderate persistent AS compared with AR. Hence, serum leptin may be a stronger predictor for childhood AS compared with AR. Among the asthmatic children, higher serum leptin levels also showed stronger associations with female gender and being overweight.

Nasal irrigation has been used as an adjunctive therapy of sinonasal disease including acute/chronic sinusitis and allergic rhinitis. Several published articles reported it also improves clinical sinus symptoms.To evaluate the effectiveness of normal saline nasal irrigation in the management of acute sinusitis in children.This was a randomized, prospective placebo-controlled study.We included 69 participants with acute sinusitis. 30 of 69 participants underwent normal saline nasal irrigation. 39 of 69 participants were not receiving nasal irrigation. All participants performed nasal peak expiratory flow rate (nPEFR) test, nasal smear examination, radiography (Water's projection) and requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQ) at the baseline visit. All participants were requested to record the symptom diary card every day and were followed-up every 1 week during this period. A physical examination, nasal smear and nPEFR were performed at each visit, and all daily diary cards collected. At the final visit, the symptoms diaries were reviewed and participants were requested to complete the PRQLQ again. The nPEFR, radiography (Water's projection) and nasal smear were also repeated.Normal saline irrigation group significantly improved mean PRQLQ values and nPEFR values at medium (T=2.816, P0.05) and final period (T=2.767, P0.05) compared with the other group. Although there were no statically significant improving rate of radiography (Water's projection) in among two groups (T=0.545, P0.05), but normal saline irrigation group was better than the other group. The improval rate of mean TSS in the irrigation group significantly improved all symptoms compared with the placebo group, in which rhinorrhea, nasal congestion, throat itching, cough and sleep quality improved. 27 of 66 (40.9%) participants with atopy, 16 of 27 (53.33%) participants underwent normal saline irrigation. Normal saline irrigation atopy group significantly improved rhinorrhea, nasal congestion, throat itching and sleep quality symptoms compared with non-irrigation atopy group. Normal saline irrigation atopy group significantly improved nPEFR values at final period (Z=2.53, P0.05).This study evidence that normal saline nasal irrigation improves Pediatric Rhinoconjunctivitis Quality of Life and decreases acute sinusitis symptoms. Nasal irrigation is an effective adjunctive treatment for pediatric acute sinusitis. Normal saline nasal irrigation in atopy children also improves allergic-related symptoms. We may need larger, longer and extended study to assess the conclusion.

Cetirizine (Zyrtec) is a potent and long-acting second-generation histamine H1- receptor antagonist for the treatment of allergic disease, such as allergic rhinitis and chronic idiopathic urticaria, in adult and child. It is a racemic mixture of levocetirizine (Xyzal) and dextrocetirizine. The purpose of this present study was to compare the efficacy of cetirizine, levocetirizine and placebo for the treatment of pediatric perennial allergic rhinitis. 74 perennial allergic rhinitis patients, aged 6 to 12 years old, assigned to 1 of 3 treatment groups for 12 weeks randomly. The effects of the three agents were compared with the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Total Symptom Score (TSS) by diary. Nasal peak expiratory flow rate (nPEFR) and laboratory examinations including serum immunoglobulin E level, eosinophil cationic protein (ECP), blood eosinophil counts and eosinophil percentage in a nasal smear were evaluated among the three groups. The results revealed that both cetirizine and levocetirizine improved TSS in comparison with the placebo group, and ceterizine appeared to be more efficacious than levocetirizine at week 8 and week 12. The PRQLQ score showed significant decreased both in cetirizine and levocetirizine group, but there was no statistic significant difference between both groups. The eosinophil proportion in a nasal smear significantly decreased among the cetirizine in comparison with the placebo group but there was no statistic significant in levocetirizine groups. Both cetirizine and levocetirizine showed significant improvement in nPEFR in comparison with the placebo group, and ceterizine appeared to be more efficacious than levocetirizine. The 12-week treatment program showed that cetirizine was more effectious than levocetirizine.

Level of Evidence: V, Case Report

Objectives: The purpose of this study was to examine the ex vivo effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the expression of urokinase-type plasminogen activator (u-PA), PA inhibitor-1 (PAI-1) and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] in the early knee osteoarthritis (OA) of humans. Design and methods: Samples of articular cartilage, meniscus and synovium of OA patients were obtained and cultured ex vivo in the presence or absence of NSAIDs (diclofenac sodium, nimesulide, celecoxib, valdecoxib, rofecoxib and etoricoxib). Results: Gelatin zymography showed that all NSAIDs generally decreased MMP-2 secretion in chondral, meniscal and synovial cultures as well as MMP-9 production in meniscal and synovial cultures. ELISA showed the inhibitions of u-PA secretion in chondral cultures by diclofenac and rofecoxib as well as in chondral and synovial cultures by nimesulide, celecoxib and etoricoxib at 48 h. On PAI-1 secretion, rofecoxib in synovial cultures and diclofenac, nimesulide, celecoxib and etoricoxib in chondral and synovial cultures had significantly suppressive effects at 48 h. Conclusions: This study clearly demonstrates that NSAIDs can down-regulate the PA/plasmin system and gelatinases expression during the early stage of knee OA, thereby possibly affect the structural progression of the disease. This inhibition seems to be independent selection of COX-1 and COX-2.

Background To test the hypothesis that naproxen, meloxicam and methylprednisolone down-regulate the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] expression during early development of osteoarthritis (OA). Methods Samples of human OA articular cartilage, meniscus and synovium were obtained at knee arthroscopy and cultured ex vivo with or without naproxen, meloxicam or methylprednisolone. MMP-2 and MMP-9 levels were evaluated by gelatin zymography and urokinase-type PA (u-PA) and PA inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA). Results Gelatin zymography revealed that naproxen, meloxicam and methylprednisolone could suppress MMP-2 secretion in all tissue cultures and MMP-9 production in meniscal and synovial cultures. ELISA showed that naproxen and meloxicam reduced u-PA secretion in chondral and synovial cultures at 48 h except in naproxen-treated chondral cultures. On PAI-1 secretion, naproxen and meloxicam had the suppressive effects in all cultures at 48 h but not in naproxen-treated meniscal cultures. Methylprednisolone also decreased u-PA secretion in chondral and synovial cultures and PAI-1 production in synovial cultures at 48 h. Conclusion Naproxen, meloxicam and methylprednisolone can down-regulate the PA/plasmin system and gelatinases expression in the early osteoarthritic knee of humans, thereby possibly have a potential structure-modifying activity in a limited use.

Background/Purpose House dust mite (HDM) is well known as one of the major indoor allergens that trigger allergic inflammation, especially asthma, and accounts for 85% of all cases. So far, asthma has been thought of as a condition of imbalance between T helper (Th)1 and Th2. Fungal immunomodulatory protein- Flammulina velutipes (FIP-fve) has been seemingly demonstrated to modulate the response to Th1 cytokine production. The aim of this study was to investigate if the oral administration of FIP-fve can inhibit HDM-induced asthma inflammation in the mouse model. Methods We divided the mice (female BALB/c, 4–6 weeks) into four groups: the prevention group, which consisted of mice sensitized by HDM (intraperitoneally on Day 1, Day 7, and Day 14, and intranasally on Day 14, Day 17, Day 21, Day 24, and Day 27) fed with FIP-fve from Day 1 to Day 14; the treatment group, which comprised mice that received treatment from Day 14 to Day 28; the positive control (PC, sensitized by HDM fed without FIP-fve) group; and the negative control group (NC, nonsensitized). Airway hyperresponsiveness induced by methacholine challenge was determined using whole-body barometric plethysmography. In addition, cytokines were analyzed from bronchoalveolar lavage fluid and serum. Histopathological studies and Liu's staining method in mice lungs were also performed. Results The results showed that both pre- and posttreated FIP-fve groups had significantly reduced airway hyperresponsiveness compared with the PC group after methacholine challenge. In addition, a significantly decreased level of HDM-specific immunoglobulin E in serum and decreased production of Th2 cytokines in bronchoalveolar lavage fluid and serum were observed in these two FIP-fve fed groups. Moreover, more decreased amounts of infiltrating inflammatory cells were present in the lungs of FIP-fve fed groups than those of the PC group. Conclusion Oral FIP-fve had an anti-inflammatory effect on the acute phase of the airway inflammatory process induced by HDM in the mouse model and might have a potentially therapeutic role for allergic airway diseases.

Background Glucosamine sulfate may have an ex vivo inhibitory effect on the plasminogen activator (PA)/plasmin system and gelatinases expression during the early development of osteoarthritis (OA). Methods We compared the levels of urokinase-type PA (u-PA), PA inhibitor-1 (PAI-1) and gelatinases (matrix metalloproteinase-2 and -9 [MMP-2 and -9]) in a series of chondral, meniscal, and synovial cultures of early OA after treatment with or without glucosamine sulfate. Results Gelatin zymography revealed that glucosamine sulfate could suppress MMP-2 secretion in chondral, meniscal and synovial cultures and also decrease MMP-9 production in synovial and meniscal cultures. ELISA data also showed the suppressive effects of glucosamine sulfate on u-PA and PAI-1 production in synovial cultures at 48 h. Conclusions Our data suggest that one of the therapeutic effects of glucosamine sulfate is to down-regulate the expressions of u-PA, PAI-1, MMP-2 and MMP-9 that underlie the destruction of articular cartilage in the early stage of OA, and therefore to delay the joint failure.

Symptomatic meniscal cysts without accompanying meniscal tears are uncommon, especially those which are formed from the anterior meniscus and invading into the infrapatellar fat pad (IPFP). The current recommended treatment for such cysts is excision through open method or arthroscopy. To our knowledge, this is the first case study about a symptomatic solitary meniscal cyst invading the IPFP that was successfully treated with needle aspiration and steroid injection after arthroscopic treatment of the associated disorders. In this paper, similar cases are also reviewed to discuss the treatment and the link between meniscal cyst and meniscal tear.

UNLABELLED Substantially more gelatinases appear in effusions of septic arthritis than in effusions of aseptic arthritis. We hypothesized there is greater plasminogen activator/plasmin activity in effusions of septic arthritis than aseptic arthritis. We examined the antigenic values of urokinase-type plasminogen activator and plasminogen activator inhibitor Type-1, cell counts, and levels of matrix metalloproteinase-2 and metalloproteinase-9 in 135 knee effusions from 80 patients with septic arthritis, rheumatoid arthritis, gouty arthritis, and osteoarthritis. Urokinase-type plasminogen activator and plasminogen activator inhibitor Type-1 antigenic values in effusions of septic arthritis were greater than those in effusions of aseptic arthritis. The increases of urokinase-type plasminogen activator and plasminogen activator inhibitor Type-1 antigenic values in effusions were associated with increased levels of prometalloproteinase-9 and the appearance of activated metalloproteinase-2. Antigenic values of urokinase-type plasminogen activator also correlated with the appearance of activated metalloproteinase-9. High plasminogen activator/plasmin activity, prometalloproteinase-9 levels, and the presence of activated metalloproteinase-2 and metalloproteinase-9 in effusions from replaced knees should increase suspicion of infection regardless of neutrophil counts. Joint aspiration reduces bacteria counts, endotoxins, proinflammatory cytokines, and matrix metalloproteinase. It also decreases the plasminogen activator/plasmin activity in effusions that may play a part in extracellular matrix destruction. LEVEL OF EVIDENCE Diagnostic study, Level III (study of nonconsecutive patients without consistently applied reference "gold" standard). See the Guidelines for Authors for a complete description of levels of evidence.

Background Prescription patterns of anti-asthma medications in children vary among doctors in different disciplines and settings, and may reflect differences in treatment outcome. The purpose of this study was to analyze the prescribing patterns of anti-asthma drugs by pediatricians, family physicians and other practitioners. Methods Data for a total of 225,537 anti-asthma prescriptions were collected from the National Health Insurance Research Database for the period from January 1, 2002 to March 31, 2002. These medications included inhaled and oral adrenergics, inhaled and oral corticosteroids, xanthine derivatives, and leuko-triene receptor antagonists prescribed by general pediatricians, family physicians and physicians in other disciplines. Results Oral p2-agonist was the most commonly prescribed drug used as monotherapy, with prescription rates of 70.4%, 46.9% and 58.0% by pediatricians, family physicians and other physicians, respectively. A xanthine derivative was the next most commonly prescribed monotherapy. Oral corticosteroid combined with oral p2-agonist, followed by oral p2-agonist combined with a xanthine derivative were the two most commonly prescribed dual-agent combined therapies by all three physician categories. The prescription rate for inhaled corticosteroid monotherapy was 7.8% by pediatricians, 5.6% by family physicians, and 8.0% by other physicians. The prescription rate for inhaled adrenergic was the highest in family physicians (14.9%), followed by the other physicians (7.2%), and was lowest in pediatricians (3.1%). Conclusion Pediatricians and family physicians appeared to share similar opinions on the medical management of children with asthma in that both most commonly prescribed oral p2-agonists and xanthine derivatives, either alone or in combination. Family physicians were least likely to prescribe an inhaled corticosteroid and most likely to prescribe an inhaled adrenergic agent.