Safety and efficacy of AK0529 in respiratory syncytial virus-infected infant patients: A phase 2 proof-of-concept trial.

Background: Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available. Methods: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment. Results: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group. Conclusions: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score. Clinical Trials Registration: NCT02654171.

Increased Circulating ADMA in Young Male Rats Caused Cognitive Deficits and Increased Intestinal and Hippocampal NLRP3 Inflammasome Expression and Microbiota Composition Alterations: Effects of Resveratrol.

Endothelial dysfunction is characterized by disturbances in nitric oxide (NO) bioavailability and increased circulating asymmetric dimethylarginine (ADMA) due to the enormous release of free radicals. Increased circulating ADMA may cause endothelial dysfunction and a variety of clinical disorders, such as liver and kidney disease. Young male Sprague-Dawley rats at postnatal day 17 ± 1 received continuous ADMA infusion via an intraperitoneal pump to induce endothelial dysfunction. Four groups of rats (n = 10 per group) were allocated: control, control and resveratrol, ADMA infusion, and ADMA infusion and resveratrol groups. Spatial memory, NLR family pyrin-domain-containing 3 (NLRP3) inflammasome, cytokine expression, tight junction proteins in the ileum and dorsal hippocampus, and microbiota composition were examined. We found cognitive deficits; increased NLRP3 inflammasome in the plasma, ileum, and dorsal hippocampus; decreased ileum and dorsal hippocampal cytokine activation and tight junction proteins; and microbiota composition alterations in the ADMA-infusion young male rats. Resveratrol had beneficial effects in this context. In conclusion, we observed NLRP3 inflammasome activation in peripheral and central dysbiosis in young male rats with increased circulating ADMA, and found that resveratrol had beneficial effects. Our work adds to the mounting evidence that inhibiting systemic inflammation is a promising therapeutic avenue for cognition impairment, probably via the gut-brain axis.

Melatonin protects against methotrexate hepatotoxicity in young rats: Impact of PI3K/Akt/mTOR signaling.

With the improvement in children's acute lymphoblastic leukemia (ALL) care, the survival rate in children ALL has improved much. Methotrexate (MTX) plays an essential role in the success of children's ALL treatment. Since hepatotoxicity is commonly reported in individuals treated with intravenous or oral MTX, our study further examined the hepatic effect following intrathecal MTX treatment, which is an essential treatment for leukemia patients. Specifically, we examined the pathogenesis of MTX hepatotoxicity in young rats and explored the impact of melatonin treatment in protection against MTX hepatotoxicity. Successfully, we found that melatonin was able to protect against MTX hepatotoxicity.

Clinical manifestations and risk factors of campylobacter gastroenteritis in children in Taiwan.

BACKGROUND: Campylobacteriosis is a common cause of bacterial gastroenteritis worldwide. This study aimed to investigate the potential risk factors, clinical and laboratory manifestations of children with campylobacteriosis under five years old in Taiwan. METHODS: This retrospective case-control study was conducted in ten major hospitals in Taiwan from 2014 to 2017. Laboratory tests and stool specimen were collected and analyzed together with questionnaire survey. Multivariate stepwise logistic regression model was used for identification of risk factors. RESULTS: A total of 64 campylobacteriosis cases were included with a median age of 25 months. We observed a less prolonged vomiting (p = 0.047), more bloody (p < 0.001) and mucoid (p = 0.005) stools, and lower AST levels (p = 0.020) in patients with campylobacteriosis. Lower parental educational attainment (p < 0.001), direct contact with acute gastroenteritis patients (p < 0.001), as well as diarrhea in the mutually cared children (p = 0.007) were linked to campylobacteriosis. Consumption of municipal water (p < 0.001), milk (OR 0.34, 95% CI 0.118-0.979), and soft beverages (OR 0.41, 95% CI 0.192-0.888) were identified as protective factors, while consuming takeout food (p = 0.032) and seafood (p = 0.019) increased risk of campylobacteriosis. CONCLUSIONS: Shorter vomiting duration, bloody and mucoid stool, and less elevated AST levels are manifestations suggestive of campylobacteriosis. Risk factors of campylobacteriosis were low parental educational attainment, direct contact with acute gastroenteritis patients, diarrhea in mutually cared children, takeout food and seafood intake. Potential protective factors include municipal water, milk, and soft beverage intake.

The clinical significance of and the factors associated with macrolide resistance and poor macrolide response in pediatric Mycoplasma pneumoniae infection: A retrospective study.

BACKGROUND: Macrolide-resistant Mycoplasma pneumoniae (MRMP) infection is increasing worldwide. However, its clinical significance is still uncertain. METHODS: The data of the Laboratory Medicine Department of Chang Gung Memorial Hospital in northern Taiwan was searched for children with molecular confirmed macrolide-susceptible Mycoplasma pneumoniae (MSMP) and MRMP infections between January 2011 and December 2018. The clinical features, laboratory data, and chest image presentations were compared between patients with MRMP and MSMP infections and between patients with good and poor macrolide response, respectively. RESULTS: Records from 158 patients were recovered. Of the enrolled patients 34 (22%) suffered MRMP infection, 27 (17%) had pleural effusions, and 47 (32%) had poor macrolide response. The macrolide resistance rate was 12% in 2011, 20% between 2015 and 2016, and 50% between 2017 and 2018, respectively. Other than a poor macrolide response, the MRMP and MSMP infections are clinically indistinguishable. The presence of pleural effusion and MRMP infections were found to be independently associated with a poor macrolide response, with odds ratios (95% confidence interval) of 14.3 (4.9-42.0) and 14.6 (5.4-40), respectively. The macrolide resistance rate of the patients with a poor macrolide response was 49% and 18% among all the patients enrolled and the patients with a pleural effusion, respectively. CONCLUSION: The macrolide resistance rate had possibly increased in recent years in Taiwan and should be continuously monitored. In addition, the macrolide response could be misleading in predicting a macrolide resistance especially for the patients with a pleural effusion.

Ecthyma Gangrenosum Secondary to Methicillin-Sensitive Staphylococcus aureus in an Atopic Child with Transient Neutropenia: A Case Report and Review of the Literature.

In addition to Pseudomonas aeruginosa, other organisms including Staphylococcus aureus have been reported to have associations with ecthyma gangrenosum (EG). There are very limited reports of Staphylococcus aureus EG causing systemic symptoms in an immunocompetent child. We present the case of an atopic child with transient neutropenia developing characteristic skin lesions of EG. Culture of the skin wounds yielded methicillin-susceptible Staphylococcus aureus (MSSA), and incisional biopsy of the skin lesions revealed aggregates of Gram-positive cocci at the subepidermal area and necrotic vasculitis but without perivascular bacterial invasion. In the literature review, seven cases of Staphylococcus aureus EG were reported, and only two were pediatric cases. From this case, we emphasize the importance of early culturing for microorganisms in cases presenting with EG. When toxin-mediated systemic symptoms accompany EG-like skin lesions, MSSA should be considered in an atopic child with transient neutropenia.

Clinical and epidemiological features in hospitalized young children with acute gastroenteritis in Taiwan: A multicentered surveillance through 2014-2017.

BACKGROUND/PURPOSE: Acute gastroenteritis (AGE) remains a significant health issue in children. The worldwide evolution of pediatric AGE pathogens had been recorded since the introduction of rotavirus vaccine. Ten years after the rotavirus vaccine was introduced to the private sectors in Taiwan, a nationwide study was conducted to elucidate the epidemiological changes among major AGE pathogens. METHODS: From January 2014 to December 2017, children younger than 5 years old, hospitalized with AGE at 10 hospitals across Taiwan were enrolled. Stool specimens were tested for Salmonella spp., Campylobacter spp., Clostridiodes difficile, norovirus, and rotavirus by polymerase chain reaction (PCR). The epidemiological and clinical information was collected. RESULTS: Enteric pathogen were detected in 1983 (42.2%) of 4700 subjects, with Salmonella spp. (12.5%) being the leading cause of AGE, followed by norovirus (11.2%), rotavirus (8.7%), C. difficile (4.2%), Campylobacter spp. (1.0%), and a mixture of at least 2 of 5 above-mentioned pathogens (4.6%). The case distributions varied across different regions. In eastern Taiwan, rotavirus (21/131, 16.0%) remained the most common pathogen detected. The rotavirus vaccine uptake rate is significantly lower in patients with rotavirus AGE. Besides, rotavirus AGE frequently occurred in children with foreign parent(s), Taiwanese indigenous people, and those with the household monthly income < NT$ 60,000. CONCLUSION: Salmonella spp. and norovirus were two major pathogens of pediatric AGE in Taiwan during 2014-17. Providing low-to middle-income households with free rotavirus vaccine nationwide and an industry-led act to reduce salmonellosis should be considered by the authorities.

Pseudopodium enriched atypical kinase 1(PEAK1) promotes invasion and of melanoma cells by activating JAK/STAT3 signals.

Pseudopodium enriched atypical kinase 1(PEAK1) is a non-receptor tyrosine kinase, which is enriched in the pseudopodia of migrating cells and plays an important role in regulating cell migration and proliferation. In the study, we investigate the therapeutic effect of PEAK1 on melanoma cells in vitro and in vivo. We used a lentiviral vector to express short hairpin RNAs (Lv-PEAK1 shRNA) for inhibiting PEAK1 expression in the melanoma SKMEL28 cells. A full-length PEAK1 gene was cloned into the pcDNA 3.1 (+) plasmid and used to infect the melanoma SKMEL19 cells. P6 (also known as Pyridines 6, EMD Chemicals), the Pan-JAK inhibitor, was used to inhibit the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway. The cell counting kit-8 (CCK-8), colony formation assay and transwell assay were used to detect cell proliferation, growth and invasion in vitro. The effect of PEAK1 on melanoma progression in vivo was also evaluated. Protein expression of PEAK1, E-cadherin, vimentin and JAK/STAT3 was measured using western blot assay or immunohistochemistry. The results showed that enforced PEAK1 expression facilitated melanoma cell growth, invasion and metastasis via activating JAK/STAT3 signals, and PEAK1 knockdown inhibited melanoma cell growth, invasion and metastasis via inactivating JAK/STAT3 signals. Further work demonstrated that P6 (500 nM) treatment reversed PEAK1-induced effect in melanoma cells. PEAK1 promotes tumorigenesis and metastasis via activating JAK/STAT3 signals, and PEAK1 knockdown reduced tumorigenesis and metastasis in melanoma via inactivating JAK/STAT3 signals, providing a novel therapeutic strategy for melanoma treatment.

Clinical characteristics and risk factors for children with norovirus gastroenteritis in Taiwan.

BACKGROUND: Norovirus is a common acute gastroenteritis (AGE) pathogen across all age groups worldwide, which is difficult to differentiate from other pathogens. This study aimed to understand the clinical characteristics and risk factors of norovirus gastroenteritis among children in Taiwan. METHODS: A prospective AGE surveillance study was conducted in children aged ≤5 years who were hospitalized in 10 major hospitals in Taiwan between 2014 and 2017. The non-AGE control group included healthy children who were matched based on age, gender, season, and geographic area. RESULTS: Overall, 674 norovirus gastroenteritis patients were enrolled. Fever (p < 0.001), mucoid stool (p < 0.001), and bloody stool (p < 0.001) occurred less frequently among norovirus gastroenteritis patients. Norovirus gastroenteritis patients yielded lower CRP values on admission (21.78 ± 36.81 vs. 46.26 ± 58.12 mg/L, p < 0.001) than non-norovirus controls. Norovirus gastroenteritis patients were associated with higher direct contact rates with AGE patients within 1 week (30.5% vs. 0.97%, p < 0.001), lower hand wash rates before meals (21.6% vs. 15.4%, p = 0.001), lower human milk (15.8% vs. 19.8%, p = 0.045) and guava consumption rates (17.8% vs. 24.3%, p = 0.002) than non-AGE participants. CONCLUSIONS: Body temperature, stool characteristics, and CRP value can help distinguish the norovirus from other pathogens. The major risk factor of norovirus AGE is contact with AGE patient. Higher frequency of hand wash, human milk, and guava intake may be protective against norovirus gastroenteritis.

Clonal spread of macrolide-resistant Mycoplasma pneumoniae sequence type-3 and type-17 with recombination on non-P1 adhesin among children in Taiwan.

OBJECTIVES: Mycoplasma pneumoniae is currently the most commonly detected bacterial cause of childhood community-acquired pneumonia in several countries. Of note, clonal expansion of macrolide-resistant ST3 occurred in Japan and South Korea. An alarming surge in macrolide resistance complicates the treatment of pneumonia. We aimed to evaluate the clinical manifestation and clonal relatedness of M. pneumoniae circulating among children in Taiwan. METHODS: We prospectively enrolled 626 children with radiologically confirmed pneumonia between 2017 and 2019. An M. pneumoniae infection was suspected on clinical grounds, and tested by real-time PCR and oropharyngeal swab cultures. We used multilocus sequence typing and whole-genome sequencing to characterize the genetic features of M. pneumoniae. RESULTS: A total of 226 children with M. pneumoniae pneumonia were enrolled. Macrolide resistance was found in 77% (174/226) of patients. Multi-locus sequence typing revealed that ST3 (n = 93) and its single-locus variant ST17 (n = 84) were the predominant clones among macrolide-resistant strains. ST17 presented clinical characteristics comparable to its ancestor ST3. On multivariate analysis, macrolide resistance (OR 3.5; 95% CI 1.4-8.5; p 0.007) was independently associated with fever >72 hours after macrolide treatment. By whole-genome sequencing, prediction analysis of recombination sites revealed one recombination site in ST3 and ST17 compared with M29 (a macrolide-sensitive ST3 strain isolated from China in 2005) containing cytadhesin MgpC-like protein, RepMP4 and RepMP5. ST17 had another recombination site containing an adhesin and RepMP2/3. CONCLUSIONS: In addition to macrolide resistance, ST3 and its ST17 variant might evolve through recombination between repetitive sequences and non-P1 cytadhesins for persistent circulation in Taiwan.

Long-term effectiveness of pentavalent and monovalent rotavirus vaccines against hospitalization in Taiwan children.

BACKGROUND: Two rotavirus vaccines (RV1 and RV5) are available on the private market in Taiwan, not included in national immunization program. Scanty reports evaluated the rotavirus vaccine effectiveness (VE) in Asian countries. METHODS: From February 2014-July 2017, we conducted a prospective case-control study in ten hospitals in Taiwan. Case-patients included children aged 8-59 months, and hospitalized with laboratory-confirmed rotavirus acute gastroenteritis (AGE). For each case patient, up to four controls, rotavirus-negative AGE or non-AGE illnesses, respectively, were matched by gender, age and enrolled date. Vaccination history was confirmed through vaccination card or hospital record. VE was calculated as (1 - odds ratio of vaccination) × 100%. RESULTS: Totally 4248 AGE patients and 2242 non-AGE controls were enrolled. A total of 330 case-patients with rotavirus AGE, 1226 rotavirus-negative AGE controls and 1122 non-AGE controls were included for analysis. Unvaccinated rate was 85.15% for rotavirus-positive cases, 42.9% for rotavirus-negative controls, and 34.31% for non-AGE controls. VE of two-dose RV1 was 84.9% (95% confidence interval [CI]:77.7%, 90.1%) for rotavirus-negative AGE and 88.9% (95% CI: 83.4%, 92.8%) for non-AGE controls, while VE of three-dose RV5 was 92.5% (95% CI: 85.1%, 96.7%) and 96.4% (95% CI: 91.9%, 98.6%), respectively. For respective vaccine, VEs were not significantly different in term of rotavirus genotypes. VEs of both vaccines declined <80% in children aged three years by combined controls. CONCLUSIONS: Both vaccines provided excellent and sustained protection against rotavirus AGE hospitalization in children in Taiwan, but the effectiveness declined slightly in children aged three years.

The potential role of pneumococcal conjugate vaccine in reducing acute respiratory inflammation in community-acquired pneumococcal pneumonia.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) reduces both invasive pneumococcal disease (IPD) and other pneumococcal infections worldwide. We investigated the impact of stepwise implementation of childhood PCV programs on the prevalence of pneumococcal pneumonia, severity of acute inflammation, and associations between breakthrough pneumonia and pneumococcal serotypes in Taiwan. METHODS: In total, 983 children diagnosed with community-acquired pneumococcal pneumonia were enrolled between January 2010 and December 2015. RESULTS: Proportions of pneumococcal vaccinations increased each year in age-stratified groups with PCV7 (32.2%) as the majority, followed by PCV13 (12.2%). The proportion of pneumococcal pneumonia decreased each year in age-stratified groups, especially in 2-5 year group. Serotype 19A is the leading serotype either in vaccinated (6.4%) or unvaccinated patients (5.2%). In particular, vaccinated patients had significantly higher lowest WBC, lower neutrophils, lower lymphocytes and lower CRP values than non-vaccinated patients (p < 0.05). After stratifying patients by breakthrough infection, those with breakthrough pneumococcal infection with vaccine coverage serotypes had more severe pneumonia disease (p < 0.05). CONCLUSION: Systematic childhood pneumococcal vaccination reduced the prevalence of community-acquired pneumococcal pneumonia, especially in 2-5 year group. Serotype 19A was the major serotype for all vaccine types in patients with pneumococcal pneumonia and severity of acute inflammatory response was reduced in vaccinated patients.

Characteristics and etiology of hospitalized pediatric community-acquired pneumonia in Taiwan.

BACKGROUND/PURPOSE: The purpose of this study was to determine the pathogens and to estimate the incidence of pediatric community-acquired pneumonia (CAP) in Taiwan. METHODS: This prospective study was conducted at eight medical centers from November 2010 to September 2013. Children aged 6 weeks to 18 years who met the radiologic criteria for pneumonia were enrolled. To detect classical and atypical bacteria and viruses, blood and pleural fluids were cultured, and respiratory specimens were examined by multiple conventional and molecular methods. RESULTS: At least one potential pathogen was identified in 705 (68.3%) cases of 1032 children enrolled, including bacteria in 420 (40.7%) cases, virus in 180 (17.4%) cases, and mixed viral-bacterial infection in 105 (10.2%) cases. Streptococcus pneumoniae (31.6%) was the most common pathogen, followed by Mycoplasma pneumoniae (22.6%). Adenovirus (5.9%) was the most common virus. RSV was significantly associated with children aged under 2 years, S. pneumoniae in children aged between 2 and 5 years, and M. pneumoniae in children aged >5 years. The annual incidence rate of hospitalization for CAP was highest in children aged 2-5 years (229.7 per 100,000). From 2011 to 2012, significant reduction in hospitalization rates pertained in children under 5 years of age, in pneumonia caused by pneumococcus, adenovirus or co-infections and complicated pneumonia. CONCLUSION: CAP related pathogens have changed after increased conjugated pneumococcal vaccination rates. This study described the latest incidences and trends of CAP pathogens, which are crucial for prompt delivery of appropriate therapy.

MUC1 confers radioresistance in head and neck squamous cell carcinoma (HNSCC) cells.

Mucin 1 (MUC1), a transmembrane glycoprotein, has shown to be as the possible prognostic marker to predict the risk of aggressive head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated the effect of MUC1 in HNSCC cells and the response to X-ray irradiation (IR). Here, we examined the impact of MUC1 overexpression or downexpression on clonogenic survival and apoptosis in response to X-ray irradiation (IR). Radioresistance and radiosensitivity were also observed in HNSCC cells that are MUC1 overexpression and MUC1 downexpression. This enhanced resistance to IR in MUC1-overexpressing cells is primarily due to increased the number of radiation-induced γH2AX/53BP1-positive foci and DNA double-strand break (DSB) repair kinetics. MUC1 overexpression repaired more than 90% of DSBs after 2 Gy radiation by 24 h compared to the empty vector overexpressing cells with less than 50% of DSB repair. However, MUC1 downexpression repaired less than 20% of DSBs compared to the empty vector-overexpresing cells. MUC1 overexpression inhibited proapoptotic protein expression, such as caspase-3, caspase-8, and caspase-9, and induced antiapoptotic protein Bcl-2, followed by resistance to IR-induced apoptosis. Our results showed that targeting MUC1 may be as a promising strategy to counteract radiation resistance of HNSCC cells.

Hospital-based surveillance of severe rotavirus gastroenteritis and rotavirus strains in young Taiwanese children.

BACKGROUND/PURPOSE: Rotavirus remains a leading cause of pediatric gastroenteritis-related hospitalization. Surveillance studies have revealed that several major rotaviral genotypes are responsible for most cases of rotavirus gastroenteritis (RVGE). This study aimed to understand the characteristics of acute gastroenteritis (AGE) caused by rotavirus in young children in Taiwan. METHODS: Ten hospitals in Taiwan were subjected to prospective hospital-based AGE surveillance during 2014-2017, and children younger than 5 years old who were hospitalized due to AGE were enrolled in the study. Medical and demographic variables were recorded and analyzed, and stool specimens were collected for rotavirus identification and genotyping via real-time RT-PCR. Non-rotavirus AGE age-matched controls were enrolled. RESULTS: Surveillance identified 4747 young children hospitalized with AGE during this study period. The median age of these patients was 2.0 years. Rotavirus was detected in stool samples from 518 patients (10.9%). The prevalent months of RVGE in 2014, 2015, and 2017, wherein the rotavirus positivity rates exceeded 30%. The most common serotypes were G3P[8] (303/518, 58.9%) and G1P[8] (86/518, 16.6%). The percentage of G3P[8] increased from 4.9% in 2014 to 74.3% in 2016 (P < 0.0001), whereas the percentage of G1P[8] decreased from 61.0% in 2014 to 22.5% in 2015 (P < 0.0001). Compared with G3P[8], G1P[8] was associated with a significantly higher C-reactive protein level (P < 0.05). CONCLUSION: Rotavirus remains a notable pathogenic etiology of childhood AGE and the G3P[8] serotype was dominant in Taiwan. This study highlighted the importance of rotavirus surveillance to ensure protective effectiveness against the circulating strains.

Prevalence and molecular characterizations of Staphylococcus aureus nasal colonization among patients in pediatric intensive care units in Taiwan.

BACKGROUND: Nasal colonization of Staphylococcus aureus is a risk factor for the pathogen transmission and the development of infections. Limited information is available on the prevalence and molecular characteristics of S. aureus colonization in pediatric intensive care unit (ICU) patients. METHODS: A cross-sectional, island-wide study was conducted in 2011. Nasal swabs were collected from pediatric ICU patients at six tertiary hospitals in Taiwan. RESULTS: Of 114 patients enrolled in total, nasal colonization of S. arueus was detected in 30 (26.3%) of them, among whom 20 (17.5%) with methicillin-resistant S. arueus (MRSA). The ST59/SCCmec IV and V clones were most common and accounted for 45% of MRSA isolates, followed by ST239/SCCmec III (25%) and ST45/SCCmec IV (20%) clones. Three ST59 MRSA isolates carried the Panton-Valentine Leukocidin genes. CONCLUSIONS: The results indicated a high prevalence of S. arueus and MRSA nasal colonization among pediatric ICU patients in Taiwan. Identification of epidemic clones warrants the implement of infection control measures to reduce colonization and prevent the dissemination of MRSA in hospitals.

Resveratrol treatment improves the altered metabolism and related dysbiosis of gut programed by prenatal high-fat diet and postnatal high-fat diet exposure.

A maternal high-fat (HF) diet sensitizes offspring to the adverse effects of postnatal HF intake and can lead to metabolic dysregulation. Resveratrol, a natural polyphenolic compound found in grapes and red wine, could help to relieve metabolic syndrome dysregulation. Since the gut microbiota is known to be closely related to metabolic homeostasis, this study aimed to investigate the impact of a combination of maternal and postweaning HF diets on the gut microbiota and whether resveratrol could relieve the gut dysbiosis associated with metabolic dysregulation. Sprague-Dawley dams were sustained on either a chow or HF diet before mating, during pregnancy and during lactation. Their offspring were randomly fed chow or a HF diet after weaning. Four experimental groups were generated: CC (maternal/postnatal chow diet), HC (maternal HF/postnatal chow diet), CH (maternal chow/postnatal high-fat diet) and HH (maternal/postnatal HF diet). A fifth group consisted of HH with resveratrol treatment. We found that both maternal and postnatal HF exposure has a distinct effect on the gut microbiota metagenome of offspring. Maternal HF diet exposure decreased plasma acetate, propionate and butyrate level, while postnatal HF diet exposure decreased plasma acetate level in adult life. The metabolic dysregulation programed by the maternal and postnatal HF diets was related to the relevant gut microbiota. Resveratrol treatment ameliorated the altered plasma propionate level related to maternal HF and postnatal HF diet treatment. Resveratrol treatment also improved most of the altered metabolic dysregulation and related dysbiosis programmed by maternal and postnatal HF diet exposure.

Effects of influenza vaccine and sun exposure time against laboratory-confirmed influenza hospitalizations among young children during the 2012-13 to 2015-16 influenza seasons.

BACKGROUND: Influenza is a major cause of acute respiratory infection burden worldwide, leading to many hospitalizations. An annual influenza vaccine is believed to be the best way to prevent influenza-related illnesses. We focused on the efficacies of other possible preventive measures such as increasing sun exposure time and dietary supplements to prevent these illnesses. METHODS: We conducted a matched-pair case-control study along with the Taiwan Pediatric Infectious Disease Alliance. We included influenza-related hospitalized patients with age ranging from 6 months to 5 years during the 2012-2013, 2013-2014, 2014-2015, and 2015-2016 influenza seasons. The controls were comparable to cases in age, sex, and residential area and had no influenza-related hospitalization records in the same season. We extracted data from vaccination histories and got the patients' guardians to complete questionnaires. Data were analyzed using conditional logistic regression. RESULTS: We enrolled 1514 children (421 influenza-infected cases and 1093 controls) in the study. We found seasonal influenza vaccination to be an independent protective factor against hospitalizations owing to influenza [p < 0.01; odds ratio (OR), 0.427; 95% confidence interval (CI), 0.306-0.594]. Children with mean sun exposure time of >7 h/week had a significantly lower risk of influenza-related hospitalizations than those with the mean sun exposure time of ≤7 h/week (p < 0.05; OR, 0.667; 95% CI, 0.491-0.906). CONCLUSIONS: Seasonal influenza vaccination effectively prevents influenza-related hospitalizations in children aged ≤5 years. Besides, >7 h of sun exposure/week may also be associated with lower risk of influenza-related hospitalizations in children.

Enterovirus 71 seroepidemiology in Taiwan in 2017 and comparison of those rates in 1997, 1999 and 2007.

BACKGROUND: During recent 20 years, enterovirus 71 (EV71) has emerged as a major concern among children, particularly in the Asia-Pacific region. To understand current EV71 serostatus, to find risk factors associated with EV71 infection and to establish future EV71 vaccine policy, we performed a seroepidemiology study in Taiwan in 2017. METHODS: After informed consent was obtained, we enrolled preschool children, 6-15-year-old students, 16-50-year-old people. They received a questionnaire and a blood sample was collected to measure the EV71 neutralization antibody. RESULTS: Altogether, 920 subjects were enrolled with a male-to-female ratio of 1.03. The EV71 seropositive rate was 10% (8/82) in infants, 4% (6/153) in 1-year-old children, 8% (7/83) in 2-year-old children, 8% (13/156) in 3-5-year-old children, 31% (38/122) in 6-11-year-old primary school students, 45% (54/121) in 12-15-year-old high school students and 75% (152/203) in 16-50-year-old people. Risk factors associated with EV71 seropositivity in preschool children were female gender, having siblings, more siblings, and contact with herpangina or hand-foot-and-mouth disease. The risk factor with EV71 seropositivity in 16-50-year-old people was having children in their families in addition to older age (p<0.001). Compared with the rates in 1997, 1999 and 2007, the rates in children were significantly lower in 2017. CONCLUSION: EV71 seropositive rates were very low, at 4% to 10%, in preschool children and not high, at 31%, in primary school students. Preschool children are highly susceptible and need EV71 vaccine most.