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Background: Nonalcoholic fatty liver disease (NAFLD) is a global problem and pediatric obesity has risen dramatically. Early NAFLD might progress to nonalcoholic steatohepatitis (NASH) or liver cirrhosis and significantly increase liver disease-related mortality. We looked for NAFLD predictors in children and adolescents.Methods: This community-based, cross-sectional study ran from December 2012 to September 2013 in southwestern Taiwan. Children <10 and >19 years old, with detected hepatic diseases, or who drank alcohol were excluded. The diagnosis of NAFLD was based on ultrasound: age, sex, anthropometric measurements, and laboratory data were evaluated for associated risks by using logistic regression analysis. Receiver operating characteristic (ROC) curves were used to determine cutoff values.Results: We enrolled one thousand, two hundred and ten children (594 males; 616 females; mean age: 15.5 ± 2.8 years). Age, anthropometric measurements, and laboratory data were significantly higher in children with NAFLD. The association between NAFLD and the waist-to-height ratio (WHtR) was significant (adjusted odds ratio: 2.6; 95% confidence interval: 1.909-3.549; P < 0.001). It indicated highly suspicion of NAFLD (sensitivity: 70.1%; specificity 76.9%) when the WHtR for children and adolescents is above the cutoff value of 0.469.Conclusions: The WHtR might be a powerful index of the severity of pediatric NAFLD. [ABSTRACT FROM AUTHOR]

Background: Neonatal bloodstream infection (BSI) is the most important cause of morbidity and mortality in the neonatal intensive care unit (NICU). Although most neonatal BSIs are primary bacteremia, some are associated with a focus of infection. This distinction is not well characterized.Methods: All patients with neonatal late-onset sepsis (LOS) between January 2006 and December 2013 were enrolled. LOS was categorized as a BSI with a concurrent focus of infection if LOS occurred before or within 24 h after the diagnosis of a specific infectious entity, and as "primary bacteremia" if no concurrent focus of infection was identified. Data concerning demographics, hospital course, microbiology, and outcomes were compared via univariate and multivariate analyses.Results: Of 948 episodes of neonatal LOS, 781 (82.4%) were primary bacteremia, whereas 167 (17.6%) were associated with a known focus of infection, including meningitis (n = 51, 5.4%), ventilator-associated pneumonia (VAP) (n = 36, 3.8%), catheter-related bloodstream infections (n = 57, 6.0%), and necrotizing enterocolitis (NEC) (n = 21, 2.2%). The majority of NEC-associated BSIs were caused by gram-negative bacilli (85.7%). Group B streptococcus accounted for nearly one-third of all meningitis cases (29.4%). Although sepsis-attributable mortality was comparable between primary bacteremia and neonatal BSIs with a focus of infection, neonatal BSIs with meningitis, VAP, and NEC had significantly higher rates of infectious complications. The independent risk factors of sepsis-attributable mortality were infectious complications (Odds ratio [OR] 6.98; 95% confidence interval [CI] 3.64-13.39, P < 0.001); history of one or more than one previous episode(s) of BSI (OR 2.40 and 7.40; 95% CI 1.21-4.74 and 3.70-14.78, P = 0.012 and <0.001, respectively); and underlying secondary pulmonary hypertension in neonates (OR 4.77; 95% CI 1.91-11.96, P = 0.001).Conclusions: A considerable proportion of neonatal LOS can be associated with known infectious foci in the NICU. The microbiologic etiology of neonatal LOS with a concurrent focus of infection is significantly different from that of primary bacteremia. Neonatal BSIs with concurrent meningitis, VAP, or NEC are significantly more likely to have infectious complications. This association independently leads to sepsis-attributable mortality. [ABSTRACT FROM AUTHOR]

Upregulation of intercellular adhesion molecule-1 (ICAM-1) involves adhesions between both circulating and resident leukocytes and the human lung epithelial cells during lung inflammatory reactions. We have previously demonstrated that curcumin-loaded polyvinylpyrrolidone nanoparticles (CURN) improve the anti-inflammatory and anti-oxidative properties of curcumin in hepatocytes. In this study, we focused on the effects of CURN on the expression of ICAM-1 in TNF-α-treated lung epithelial cells and compared these to the effects of curcumin water preparation (CURH). TNF-αinduced ICAM-1 expression, ROS production, and cell-cell adhesion were significantly attenuated by the pretreatment with antioxidants (DPI, APO, or NAC) and CURN, but not by CURH, as revealed by western blot analysis, RT-PCR, promoter assay, and ROS detection and adhesion assay. In addition, treatment of TNF-α-treated cells with CURN and antioxidants also resulted in an inhibition of activation of p47 phox and phosphorylation of MAPKs, as compared to that using CURH. Our findings also suggest that phosphorylation of MAPKs may eventually lead to the activation of transcription factors. We also observed that the effects of TNF-α treatment for 30 min, which includes a significant increase in the binding activity of AP-1 and phosphorylation of c-jun and c-fos genes, were reduced by CURN treatment. In vivo studies have revealed that CURN improved the anti-inflammation activities of CURH in the lung epithelial cells of TNF-α-treated mice. Our results indicate that curcumin-loaded polyvinylpyrrolidone nanoparticles may potentially serve as an anti-inflammatory drug for the treatment of respiratory diseases. [ABSTRACT FROM AUTHOR]

Attention-deficit hyperactivity disorder (ADHD), a common neurobehavioural disorder characterized by inattention, hyperactivity and impulsivity, is a chronic disorder and often persists into adulthood. CNS stimulants have been the most well known treatment for ADHD for several decades due to their high effectiveness, good safety profiles and relatively minor adverse effects. Non-stimulant agents, including atomoxetine, extended-release guanfacine and extended-release clonidine (US FDA approved), and several non-FDA-approved agents, such as bupropion and tricyclic antidepressants (TCAs), were recently proven to be effective alternatives to the stimulants in several open-label and placebo-controlled trials. However, most medication trials for ADHD have been short term and thus have not provided information on the long-term outcomes of ADHDtreatment. Since the medical treatment of many children with ADHD, especially those with more severe symptoms or co-morbid disorders, has to be continued for several years, recent studies have shifted their focus from the acute effectiveness of stimulants or non-stimulant drugs to the long-term outcomes of medications for ADHD. Evidence has shown that stimulants, along with the non-stimulants atomoxetine and extended-release guanfacine, are continuously effective for 24-month treatment periods with few and tolerable adverse effects. [ABSTRACT FROM AUTHOR]

Introduction: Atherosclerotic cardiovascular disease is associated with a high mortality rate due to vascular calcification. The role of fetuin-A in aortic arch calcification (AAC) is less well understood., Methods: An analysis of secondary biomarkers was performed on 800 individuals from the biobank using the community database. AAC was defined by radiologists based on imaging. Multiple variables logical analysis was used for risk analysis., Results: A total of 736 individual samples were collected based on age and gender. The average age is 65 ± 10 years, and half the population comprises men. In spite of similar body weight, renal function, and hepatic function, the AAC group had higher blood pressure and fetuin-A levels independently: systolic blood pressure (SBP) index ≥130 mmHg [adjusted odds ratio (aOR) 1.85, 95% confidence interval (CI) 1.34-2.57, p  = 0.002] and fetuin-A (aOR 0.62, 95% CI 0.50-0.76, p  < 0.001). Moreover, it is evident that AAC can be predicted more accurately when combined with SBP ≥130 mmHg and a low fetuin-A level (<358 μg/ml: aOR 5.39, 95% CI 3.21-9.08) compared with the reference., Conclusion: Low fetuin-A levels are significantly correlated with AAC while there is an increased association between vascular calcification and coexisting hypertension., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Lin, Lin, Shi, Lin, Lin, Yang, Liao, Chen, Tsai and Lin.)

Backgound: Conventional diagnosis of invasive fungal disease from blood cultures is often notoriously delayed and inadequately sensitive. We aimed to develop a universal primers-based polymerase chain reaction (PCR) assay and restriction fragment length polymorphisms (RFLP) for rapid identification of invasive fungal disease (IFD)., Methods: We evaluated 16 clinical fungal species using a combination of PCR assays with 3 different restriction endonucleases targeting various internal transcribed spacer (ITS) regions and high resolution melting analysis (HRMA). Serial samples from 75 patients suspected to have IFD were analyzed for clinical verification., Results: We have designed a universal PCR capable of amplifying a portion of the 18S rRNA gene of 16 clinically important fungal species. The restriction patterns of most PCR products generated by EcoRI or double digested by ClaI and AvaI were different, except Aspergillus niger and Aspergillus flavus had a similar pattern, and Aspergillus fumigatus and Aspergillus terreus had a similar pattern. All these species had a unique melting curve shape using the HRMA. Both HRMA and universal PCR had adequate sensitivity, and all sixteen reference fungal species can be clearly distinguished by the universal PCR-RFLP-HRMA assay. With a reference library of 176 clinically relevant fungal strains, and 75 clinical samples from patients with suspicious IFD were tested, our assay identified 100% and 61.1% of isolates from the reference library and clinical samples, respectively., Conclusions: Universal PCR and RFLP coupled with HRMA could be a highly discriminative and useful molecular diagnostic that could enhance the current diagnostic, treatment, and surveillance methods of invasive fungal disease., (Copyright © 2019. Published by Elsevier B.V.)

Background: Group B Streptococcus (GBS) is an important pathogen that causes high mortality and morbidity in young infants. However, data on clinical manifestations between different GBS serotypes and correlation with molecular epidemiology are largely incomplete. The aim of this study was to determine the serotype distribution, antimicrobial resistance, clinical features and molecular characteristics of invasive GBS isolates recovered from Taiwanese infants., Methods: From 2003 to 2017, 182 non-duplicate GBS isolates that caused invasive disease in infants less than one year of age underwent serotyping, multilocus sequence typing (MLST) and antibiotic susceptibility testing. The clinical features of these infants with GBS disease were also reviewed., Results: Of the 182 patients with invasive GBS disease, 41 (22.5%) were early-onset disease, 121 (66.5%) were late-onset disease and 20 (11.0%) were late late-onset disease (> 90 days of age). All these patients were treated with effective antibiotics on time. Among them, 51 (28.0%) had meningitis, 29 (16.0%) had neurological complications, 12 (6.6%) died during hospitalization, and 15 (8.8%) out of 170 patients who survived had long-term neurological sequelae at discharge. Serotype III GBS strains accounted for 64.8%, followed by serotype Ia (18.1%) and Ib (8.2%). MLST analysis revealed 11 different sequence types among the 182 isolates and ST-17 was the most dominant sequence type (56.6%). The correlation between serotype III and ST17 was evident, as ST17 accounted for 87.3% of all serotype III isolates. There was an obvious increasing trend of type III/ST-17 GBS that caused invasive disease in infants. All isolates were susceptible to penicillin, cefotaxime, and vancomycin, while 68.1 and 65.9% were resistant to erythromycin and clindamycin, respectively., Conclusions: Despite timely and appropriate antibiotic treatment, a significant proportion of invasive GBS disease still inevitably causes adverse outcomes. Further study to explore preventive strategies and development of serotype-based vaccines will be necessary in the future.

Background: High-dose steroids and intravenous immunoglobulin (IVIG) are controversial treatments for pediatric patients with acute myocarditis. This study aimed to investigate their efficacies in the Taiwanese pediatric population., Methods: This study evaluated 5563 acute myocarditis patients from the Taiwan's National Health Insurance Research Database and identified 1542 pediatric patients hospitalized for acute myocarditis between January 1, 2001 and December 31, 2011. The exclusion criteria were age of > 11 years, associated cardiovascular comorbidities, autoimmune disease, malignancy before the index hospitalization, extracorporeal membrane oxygenation, intra-aortic balloon pumping, and dual therapy using IVIG and high-dose steroids., Results: After 2:1 propensity score matching, we identified 208 subjects without steroid therapy and 104 subjects who received high-dose steroids. The mean age in that cohort was 2.6 ± 2.9 years, and high-dose steroid therapy had no significant effects on major in-hospital complications and post-discharge outcomes. After 2:1 propensity score matching, we identified 178 subjects without IVIG therapy and 89 subjects who received IVIG. The mean age in that cohort was 2.0 ± 2.1 years, and IVIG had no significant effects on the major outcomes., Conclusions: The present study revealed that high-dose steroid or IVIG therapy had no significant effects on major in-hospital complications, late heart failure hospitalization, and long-term mortality.

Background: Candidemia in children caused by non-albicans Candida (NAC) spp is increasing in prevalence, but the relevant information is limited., Methods: All isolates of pediatric candidemia from a medical center in Taiwan between 2003 and 2015 were enrolled. The characteristics of patients with NAC and Candida albicans candidemia (CAC) were compared., Results: Among the 319 episodes of candidemia occurring in 262 patients, C albicans accounted for 46.4%. The NAC and CAC groups had no significant differences in demographics, underlying diseases, most risk factors, and clinical characteristics. Patients in the NAC group were significantly more likely to have fluconazole exposure (14.0% vs 6.8%, respectively; P = .045), and NAC species accounted for 70.2% of all recurrent episodes. NAC candidemia had a longer duration of candidemia (median, 3.0 vs 1.0 days after effective antifungal treatment, respectively; P = .001), slower responses to antifungal treatment, and a higher rate of treatment failure than CAC. However, the 2 groups had similar 30-day candidemia-attributable mortality rates. After multivariate logistic regression, longer duration of central venous catheter was the independent risk factor for NAC candidemia in children (odds ratio, 1.21; 95% confidence interval, 1.08-1.35 for every 10-day increment)., Conclusions: NAC species collectively have emerged as the predominant pathogens of candidemia in children. Prolonged use of a central venous catheter is associated with an increased risk of candidemia caused by NAC species., (Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Staphylococcus aureus (S. aureus) can lead to many life-threatening diseases. It has the ability to invade normal endovascular tissue. The molecular mechanisms and pathological changes of endothelial cells after S. aureus infection are of interest, but the basic understanding of how S. aureus destroys this barrier is not clear. Here, we showed that S. aureus enhanced COX-2 expression and prostaglandin E 2 (PGE 2 ) secretion in human aortic endothelial cells (HAECs). In addition, S. aureus induced PGE 2 /interleukin-6 (IL-6)/matrix metallopeptidase-9 (MMP-9)-dependent cell migration. S. aureus-induced COX-2, IL-6, and MMP-9 levels were inhibited by transfection with siRNA of Toll-like receptor 2 (TLR2), p38, p42, p44, p50, or p65. S. aureus also induced p38 MAPK, ATF2, ERK1/2, and NF-κB p65 activation. Interestingly, we proved that S. aureus decreased intracellular generation of reactive oxygen species (ROS), which suggests that the inhibition of ROS production promoted inflammatory responses. Finally, we showed that S. aureus enhanced a variety of biomarkers of inflammation in cardiovascular diseases. However, the free radical scavenger (MCI-186) or antioxidant (N-acetyl-L-cysteine, NAC) markedly enhanced S. aureus-induced COX-2 mRNA levels in the aorta tissues. Taken together, these findings established that S. aureus promoted aorta inflammation via activation of p38 MAPK, ERK1/2, and NF-κB and inhibition of ROS generation., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Staphylococcus aureus (S. aureus) can often lead to many life-threatening diseases. It has the ability to invade normal endovascular tissue. Acute inflammation and its resolution are important to ensure bacterial clearance and limit tissue injury. Carbon monoxide (CO) has been shown to exert anti-inflammatory effects in various tissues and organ systems. In our study, we investigated the effects and the mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on S. aureus-induced inflammatory responses in human aortic endothelial cells (HAECs). We proved that S. aureus induced cyclooxygenase-2 (COX-2)/prostaglandin E 2 (PGE 2 )/interleukin-6 (IL-6)/matrix metallopeptidase-9 (MMP-9) expression and cell migration, which were decreased by CORM-2. Moreover, CORM-2 had no effects on TLR2 mRNA levels in response to S. aureus. Interestingly, we proved that S. aureus decreased intracellular ROS generation, suggesting that the inhibition of ROS further promoted inflammatory responses. However, CORM-2 significantly inhibited S. aureus-induced inflammation by increasing intracellular ROS generation. S. aureus-induced NF-κB activation was also inhibited by CORM-2. Finally, we proved that S. aureus induced levels of the biomarkers of inflammation in cardiovascular diseases, which were inhibited by CORM-2. Taken together, these results suggest that CORM-2 inhibits S. aureus-induced COX-2/PGE 2 /IL-6/MMP-9 expression and aorta inflammatory responses by increasing the ROS generation and reducing the inflammatory molecules levels., (Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Many uncommon Candida spp. (species other than C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and C. krusei) have been shown to emerge in tertiary care facilities. We aimed to investigate these uncommon candidemia in children. Forty-six cases of candidemia caused by uncommon Candida spp. were identified during 2003-2015 from a medical center in Taiwan. The most common specie was C. guilliermondii (31.2%), followed by C. lusitaniae (18.8%) and C. metapsilosis (18.8%). These cases were analyzed and compared with 148 episodes of C. albicans candidemia. The incidence density of uncommon Candida spp. candidemia and the proportion to all candidemia episodes increased substantively during the study period. Prior exposure to azoles was uncommon in the 30 days prior to infection, but fluconazole resistant strains were significantly more common (n = 19, 41.3%). The increased incidence density of uncommon Candida spp. candidemia was associated with increasing use of antifungal agents. No differences in demographics, underlying comorbidities, risk factors, clinical features, dissemination, and 30-day mortality were found between uncommon Candida spp. and C. albicans candidemia. Patients with uncommon Candida spp. candidemia were more likely to require modifications in antifungal treatment and receive echinocandin drugs (43.5% vs 21.6%, p = 0.007). Candidemia caused by uncommon Candida spp. had poorer response to antifungal treatment, led to longer duration of candidemia (median 4.0 versus 2.5 days, p = 0.008), and had a higher treatment failure rate (56.5% vs 38.5%, p = 0.040).

Thrombospondin (TSP)-2, a matricellular glycoprotein of the TSP family, regulates multiple biological functions, including proliferation, angiogenesis, cell adhesion, and extracellular matrix (ECM) modeling. The clinical relevance of TSP-2 has been explored in many different cancers. TSP-2 expression levels vary between different cancer types, and their role in tumor progression remains controversial. Although previous studies have reported higher serum TSP-2 levels in patients with non-small cell lung cancer, the role of TSP-2 in lung cancer progression remains to be addressed. A total of 585 lung adenocarcinoma datasets, including mRNA sequencing and clinical data, were retrieved from The Cancer Genome Atlas (TCGA). Forty paired adjacent normal tissues and lung tumor tissue datasets were used to examine TSP-2 expression levels. Tumor microarray were performed with immunohistochemical staining to examine TSP-2 expression in lung cancer patients. Transwell migration assay, quantitative real-time PCR and Western blot were used to investigate molecular mechanism of TSP-2 in lung cancer cell. TSP-2 promotes matrix metalloproteinase-13 (MMP-13) expression, cell migration, and cell invasion by mediating integrin αvβ3/FAK/Akt/NF-κB signal transduction. Using TSP-2 knockdown stable cell lines, we found that TSP-2 knockdown reduces MMP-13 expression and cell mobility. When we manipulated the tumor tissue microarray and TCGA datasets to investigate the clinical relevance of TSP-2, we found high TSP-2 expression levels in lung cancer specimens. The present study demonstrates that TSP-2 regulates cell mobility through MMP-13 expression in lung cancer cells. In addition, TSP-2 expression was associated with MMP-13 expression and poor prognosis in lung cancer. TSP-2 may therefore be a promising novel target for lung cancer treatment., (Copyright © 2018. Published by Elsevier Inc.)

Background: Invasive candidiasis differs greatly between children and neonates. We aimed to investigate the different therapeutic approaches and their effects on treatment outcomes of these two groups., Methods: Episodes of neonatal invasive candidiasis were compared with non-neonatal pediatric episodes during a 12-year cohort study. Clinical isolates were documented by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and DNA sequencing, and antifungal susceptibility testing was performed., Results: A total of 342 episodes of invasive candidiasis (113 neonatal and 229 non-neonatal pediatric episodes) in 281 pediatric patients (96 neonates and 185 children) were identified. Candida albicans was the most common pathogen causing invasive candidiasis in neonates and children (47.8% vs. 44.1%). The antifungal susceptibility profiles were not significantly different between neonates and children. More neonates received amphotericin B as therapy, whereas more children received fluconazole or caspofungin. Compared with children, neonates had a significantly longer duration of fungemia, higher rates of septic shock (34.5% vs. 21.8%; P = 0.013), sepsis-attributable mortality (28.3% vs. 17.5%; P = 0.024) and in-hospital mortality (42.7% vs. 25.4%; P = 0.004) than children. Independent risk factors for treatment failure of invasive candidiasis were septic shock (odds ration [OR] 16.01; 95% confidence interval [CI] 7.64-33.56; P <  0.001), delayed removal of intravenous catheter (OR 6.78; 95% CI 2.80-17.41; P <  0.001), renal failure (OR 5.38; 95% CI 1.99-14.57; P = 0.001), and breakthrough invasive candidiasis (OR 2.99; 95% CI 1.04-8.67; P = 0.043)., Conclusions: Neonatal invasive candidiasis has worse outcomes than non-neonatal pediatric candidiasis. Neonatologists and pediatricians must consider age-specific differences when developing treatment and prevention guidelines, or when interpreting studies of other age groups.

Ang II has been involved in the pathogenesis of cardiovascular diseases, and matrix metalloproteinase-9 (MMP-9) induced migration of human aortic smooth muscle cells (HASMCs) is the most common and basic pathological feature. Carbon monoxide (CO), a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory effects in various tissues and organ systems. In the present study, we aimed to investigate the effects and underlying mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on Ang II-induced MMP-9 expression and cell migration of HASMCs. Ang II significantly up-regulated MMP-9 expression and cell migration of HASMCs, which was inhibited by transfection with siRNA of p47 phox , Nox2, Nox4, p65, angiotensin II type 1 receptor (AT1R) and pretreatment with the inhibitors of NADPH oxidase, ROS, and NF-κB. In addition, Ang II also induced NADPH oxidase/ROS generation and p47 phox translocation from the cytosol to the membrane. Moreover, Ang II-induced oxidative stress and MMP-9-dependent cell migration were inhibited by pretreatment with CORM-2. Finally, we observed that Ang II induced IL-6 release in HASMCs via AT1R, but not AT2R, which could further caused MMP-9 secretion and cell migration. Pretreatment with CORM-2 reduced Ang II-induced IL-6 release. In conclusion, CORM-2 inhibits Ang II-induced HASMCs migration through inactivation of suppression of NADPH oxidase/ROS generation, NF-κB inactivation and IL-6/MMP-9 expression. Thus, application of CO, especially CORM-2, is a potential countermeasure to reverse the pathological changes of various cardiovascular diseases. Further effects aimed at identifying novel antioxidant and anti-inflammatory substances protective for heart and blood vessels that targeting CO and establishment of well-designed in vivo models properly evaluating the efficacy of these agents are needed., (Copyright © 2017. Published by Elsevier B.V.)

Human fibroblast-like synoviocytes (FLSs) play a role in joint synovial inflammation in rheumatoid arthritis (RA). Some evidence indicates that particulate matter (PM) in air pollution could contribute to the progression of RA. However, more research is needed to clarify this relationship. Up-regulation of cyclooxygenase (COX)-2 and its metabolite prostaglandin E 2 (PGE 2 ) are implicated in various inflammatory diseases. Resveratrol, a polyphenol found mainly in grapes and red wine, has antioxidant and anti-inflammatory activities. In the present study, we demonstrated that resveratrol reduced PM-induced COX-2/PGE 2 expression in human FLSs, and attenuated PM-enhanced NADPH oxidase activity and ROS generation. In addition, PM induced Akt, ERK1/2, or p38 MAPK activation, which was inhibited by resveratrol. Finally, we demonstrated that PM enhanced NF-κB p65 phosphorylation and the NF-κB promoter activity, which were reduced by pretreatment with a ROS inhibitor or resveratrol. Thus, we concluded that resveratrol functions as a suppressor of PM-induced inflammatory signaling pathways by inhibiting COX-2/PGE 2 expression., (Copyright © 2017. Published by Elsevier Ltd.)

Exposure to particulate matter (PM), a major form of air pollution, can induce oxidative stress and inflammation and may lead to many diseases in various organ systems including the skin. Eupafolin, a flavonoid compound derived from Phyla nodiflora, has been previously shown to exhibit various pharmacological activities, including antioxidant and anti-inflammatory effects. Unfortunately, eupafolin is characterized by poor water solubility and skin penetration, which limits its clinical applications. To address these issues, we successfully synthesized a eupafolin nanoparticle delivery system (ENDS). Our findings showed that ENDS could overcome the physicochemical drawbacks of raw eupafolin with respect to water solubility and skin penetration, through reduction of particle size and formation of an amorphous state with hydrogen bonding. Moreover, ENDS was superior to raw eupafolin in attenuating PM-induced oxidative stress and inflammation in HaCaT keratinocytes, by mediating the antioxidant pathway (decreased reactive oxygen species production and nicotinamide adenine dinucleotide phosphate oxidase activity) and anti-inflammation pathway (decreased cyclooxygenase-2 expression and prostaglandin E2 production through downregulation of mitogen-activated protein kinase and nuclear factor-κB signaling). In summary, ENDS shows better antioxidant and anti-inflammatory activities than raw eupafolin through improvement of water solubility and skin penetration. Therefore, ENDS may potentially be used as a medicinal drug and/or cosmeceutical product to prevent PM-induced skin inflammation.

Attention deficit hyperactivity disorder (ADHD) affects approximately 5 % of children and adolescents, and sleep problems are common in these patients. There is growing evidence informing the significant importance of sleep problems in youth with ADHD. The sleep problems in children with ADHD include specific sleep disorders and sleep disturbances due to comorbid psychiatric disorders or ADHD medications. The specific sleep disorders of ADHD children include behaviorally based insomnia, sleep-disordered breathing, and restless legs syndrome/periodic limb movement disorder. Current practices on the management of sleep problems for ADHD children are based mostly on expert consensus, whereas more evidence-based literature can be found only recently. Assessment of the sleep conditions in ADHD children before initiation of pharmacotherapy is the currently recommended guideline, and good sleep hygiene can be considered as the first-line treatment option. In addition to modifying the dose regimens, formulation, or alternative stimulants when sleep problems are encountered in ADHD children, atomoxetine, once daily guanfacine extended release, and melatonin are potential choices for ADHD children with more severe sleep problems. In this review, we aimed to provide the most updated information, preferably based on meta-analyses, systemic review, and randomized controlled trials published in the latest 3 years, in order to be clinically useful for practitioners and clinicians.

Background: Gram-negative bacillary (GNB) bloodstream infections account for 20%-30% of neonatal late-onset sepsis (LOS). We aimed to identify the incidence, clinical characteristics, and risk factors for adverse outcomes in neonates with GNB LOS., Methods: All patients with GNB LOS admitted to the neonatal intensive care units (NICUs) of a university-affiliated teaching hospital in Taiwan from January 1, 2004-December 31, 2011, were enrolled. A case-control-control study was performed to evaluate risk factors for acquisition of neonatal GNB LOS., Results: Of the 5,010 neonates, 290 (5.8%) had a total of 346 episodes of GNB LOS (36.7% of total LOS), with an incidence rate of 13.6 per 10,000 neonate hospital days. The overall mortality rate was 17.6% (51/290), and the sepsis attributable mortality rate was 9.8% (34/346 episodes). After multivariate logistic regression analysis, neonates with prolonged use of total parenteral nutrition (adjusted odds ratio [OR] = 1.53; 95% confidence interval [CI], 1.02-2.29; P = .041) were independently associated with acquisition of GNB LOS. The independent predictors of in-hospital mortality were Pseudomonas aeruginosa etiology (OR = 11.45; 95% CI, 2.83-46.24) and underlying secondary pulmonary hypertension (OR = 18.02; 95% CI, 3.28-98.89), renal disease (OR = 17.16; 95% CI, 2.96-99.38), and neuromuscular comorbidities (OR = 2.72; 95% CI, 1.06-7.00)., Conclusion: Given the higher illness severity and sepsis-attributable mortality rate of neonatal GNB LOS in the NICU, strategies to reduce the incidence need to be addressed urgently., (Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: An episode of breakthrough bacteremia, which was defined as positive blood cultures despite appropriate antibiotic therapy, imposes a treatment challenge in the neonatal intensive care unit (NICU)., Methods: All episodes of breakthrough bacteremia from a tertiary level NICU in Taiwan between 2004 and 2011 were analyzed and compared with nonbreakthrough bacteremia., Results: Breakthrough bacteremia was identified in 7.6% (72/942) of neonatal bacteremia, and 43 (59.7%) occurred as recurrent episodes. Gram-negative organisms (41.7%) and fungi (15.3%) accounted for more than half of all microorganisms in breakthrough bacteremia. Compared with nonbreakthrough bacteremia, breakthrough bacteremia was significantly associated with more severe disease, was more likely to require aggressive therapies, and had a higher rate of infectious complications. Previous use of broad-spectrum antibiotics (odds ratio [OR], 7.54; P < .001) and particular microbial etiologies (Pseudomonas aeruginosa: OR, 4.40; P = .025; fungi: OR, 2.70; P = .013) were independent risk factors for developing breakthrough bacteremia. The crude sepsis-attributable mortality rate was greater in breakthrough bacteremia episodes (16.7% vs 6.4%; P = .004), and this condition was independently associated with an increased risk of death (OR, 2.14; 95% confidence interval, 1.04-4.40; P = .040)., Conclusion: Breakthrough bacteremia is not uncommon (7.6% of all bacteremia) in NICUs and represents a more severe form of neonatal bacteremia that is independently associated with an increased risk of death., (Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Eupafolin, a major active component found in the methanol extracts of Phyla nodiflora, has been used to treat inflammation of skin. We examined its effects on cyclooxygenase-2 (COX-2) expression in LPS-treated human dermal fibroblasts. Lipopolysaccharide (LPS) significantly increased prostaglandin-E2 (PGE2) production associated with increased COX-2 expression in Hs68 cells. This effect was blocked by eupafolin, TLR-4 antibody, antioxidants (APO and NAC), as well as inhibitors, including U0126 (ERK1/2), SB202190 (p38), SP600125 (JNK1/2), and Tanshinone IIA (AP-1). In gene regulation level, qPCR and promoter assays revealed that COX-2 expression was attenuated by eupafolin. In addition, eupafolin also ameliorated LPS-induced p47 phox activation and decreased reactive oxygen species (ROS) generation and NADPH oxidase (Nox) activity. Moreover, pretreatment with eupafolin and APO led to reduced LPS-induced phosphorylation of ERK1/2, JNK, and p38. Further, eupafolin attenuated LPS-induced increase in AP-1 transcription factor binding activity as well as the increase in the phosphorylation of c-Jun and c-Fos. In vivo studies have shown that in dermal fibroblasts of LPS treated mice, eupafolin exerted anti-inflammation effects by decreasing COX-2 protein levels. Our results reveal a novel mechanism for anti-inflammatory and anti-oxidative effects of eupafolin that involved inhibition of LPS-induced ROS generation, suppression of MAPK phosphorylation, diminished DNA binding activity of AP-1 and attenuated COX-2 expression leading to reduced production of prostaglandin E2 (PGE2). Our results demonstrate that eupafolin may be used to treat inflammatory responses associated with dermatologic diseases., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: We aimed to characterize the clinical manifestations and outcomes of patients with Acinetobacter baumannii bacteremia in the neonatal intensive care unit (NICU)., Methods: All patients with A baumannii bacteremia in our NICU from 2004 to 2010 were reviewed. A matched case-control study was performed by comparing each case of A baumannii to 2 uninfected controls and all cases of Escherichia coli and Klebsiella bacteremia, respectively., Results: Thirty-seven cases with A baumannii bacteremia were identified. Multidrug-resistant isolate was noted in only 2 cases (5.4%), and the overall mortality rate was 8.1%. Compared with matched, uninfected controls, infants with A baumannii were more likely to have had a central vascular catheter (CVC) (P = .009), use of total parenteral nutrition (TPN) (P = .021), longer duration of ventilator use (P = .002), and hospitalization (P = .010). Compared with E coli or Klebsiella bacteremia, infants with A baumannii bacteremia had lower birth weight (median of 1,090 g vs 1,300 g, P = .044) and a higher rate of CVC and TPN use (both P < .001) at the time of infection., Conclusion: A baumannii bacteremia occurs endemically or sporadically in the NICU, primarily in low-birth-weight infants on TPN use and with CVC in situ. Although A baumannii does not often cause mortality, and multidrug-resistant A baumannii is uncommon, it contributes significantly to longer hospitalization., (Crown Copyright © 2014. Published by Mosby, Inc. All rights reserved.)

Objective: To investigate the 6-month neurodevelopmental outcomes of prematurely born neonates and find the determining neonatal factors of minor neurological dysfunctions (MNDs)., Study Design: We examined data collected prospectively on 151 infants born before 37th week of gestation in 2009-2010 who were assessed at 6 months corrected age with the Bayley Scales of Infant Development-2nd Edition (BSID-II) and the Denver Developmental Screening Test (DDST)., Results: Of 151 neonates born before 37 weeks, 20 (13.2%) had MNDs at 6 months corrected age. These proportions were 21.6%, 13.2%, and 8.2% for neonates born before 28 weeks, 29 weeks to 32 weeks, and 33 weeks to 36 weeks, respectively. Half of neonates with MNDs have a birth body weight of less than 1000g. BSID-II and DDST are highly correlated in assessing the MNDs of premature neonates at 6 months corrected age. MND was independently associated with postnatal corticosteroid use (odds ratio [OR], 11.2; 95% confidence interval [CI], 1.9-66.0, P=0.008) and cholestasis (OR, 6.2; 95% CI, 1.16-33.1, P=0.033)., Conclusions: Premature neonates, even those born at 33 to 36 weeks, are found to have MNDs as early as 6 months corrected age by BSID-II and DDST, with risk increasing as gestation decreases., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Synchronous multifocal osteosarcoma (SMOS), defined as more than one bone lesion at presentation, is a rare variant form of osteosarcoma. The onset is usually in childhood or early adolescence without pulmonary metastasis. The prognosis has been dismal. Whether SMOS represents a true multicentic origin or merely bone-to-bone metastases remains controversial. Here, we report a case of SMOS in a 10-year-old girl, with the dominant primary sclerotic tumor arising from the right distal femur. Despite aggressive chemotherapy and limb salvage surgery, she died of progressive multiple axial skeletal and symmetrical metaphyseal long bone diseases within one year after diagnosis. No pulmonary metastasis was found before she died.