Aim
The aim of this study was to describe antibiotic exposure in Australian infants during the first year of life, focusing on antibiotic class, indication, risk factors associated with exposure and ...comparison with international counterparts.
Methods
The Barwon Infant Study is a birth cohort study (n = 1074) with an unselected antenatal sampling frame from a large regional centre in Victoria, Australia. Longitudinal data on infection and medication were collected at 1, 3, 6, 9 and 12 months by parental questionnaire and from general practitioner and hospital records. Predictors of questionnaire non‐completion were identified. A total of 660 infants with complete serial data were comprehensively examined. Antibiotic exposure was calculated as (i) antibiotic prescriptions and (ii) antibiotic days‐exposed per person‐year.
Results
Mean antibiotic prescription rate was 0.92 prescriptions (95% confidence interval (CI), 0.83–1.02) per person‐year, with the highest rates in those aged <1 month (1.50 (95% CI, 1.09–1.91) per person‐year). A total of 50.0% of infants were exposed to at least one antibiotic in their first year of life. Increasing number of siblings was associated with increased antibiotic exposure. Penicillin with extended spectrum (365 of 661 antibiotic prescriptions, 52.6%) and cephalosporins (12.0%) were the most frequently prescribed antibiotics. One fifth of antibiotics were prescribed for respiratory tract infections and bronchiolitis.
Conclusion
Australian infants in this large population‐based study are exposed to considerably more antibiotics than the majority of their international counterparts. Interventions aimed at addressing avoidable prescribing by medical practitioners and modifiable risk factors associated with antibiotic exposure may reduce antibiotic use.
Background
One of the major unresolved issues in treating pain is the paradoxical hyperalgesia produced by opiates, and accumulating evidence implicate that EphBs receptors and ephrinBs ligands are ...involved in mediation of spinal nociceptive information and central sensitization, but the manner in which ephrinB/EphB signalling acts on spinal nociceptive information networks to produce hyperalgesia remains enigmatic. The objective of this research was to investigate the role of ephrinB/EphB signalling in remifentanil‐induced hyperalgesia (RIH) and its downstream effector.
Methods
We characterized the remifentanil‐induced pain behaviours by evaluating thermal hyperalgesia and mechanical allodynia in a rat hind paw incisional model. Protein expression of EphB1 receptor and ephrinB1 ligand in spinal dorsal horn cord was determined by Western blotting, and Fos was determined by immunohistochemistry assay, respectively. To figure out the manner in which ephrinB/EphB signalling acts with N‐methyl‐d‐aspartic acid (NMDA) receptor, we used MK‐801, an antagonist of NMDA receptor, trying to suppressed the hyperalgesia induced by ephrinB1‐Fc, an agonist of ephrinB/EphB.
Results
Continuing infusion of remifentanil produced a thermal hyperalgesia and mechanical allodynia, which was accompanied with increased protein expression of spinal‐level EphB1 receptor, ephrinB1 ligand and Fos; what appeared above was suppressed by pretreatment with EphB1‐Fc, an antagonist of ephrinB/EphB or MK‐801, and increased pain behaviours induced by intrathecal injection of ephrinB1‐Fc, an agonist of ephrinB/EphB, were suppressed by MK‐801.
Conclusions
Our findings indicated that ephrinB/EphB signalling is involved in RIH. EphrinB/EphB signalling might be the upstream of NMDA receptor.
Background Infections with Streptococcus pneumoniae (pneumococcus) are a cause of significant child mortality. Pneumococcal glycoconjugate vaccines are expensive and provide limited serotype ...coverage. The 23-valent pneumococcal polysaccharide vaccine (Pneumovax) might provide wider serotype coverage but is reported to be weakly immunogenic in children less than 2 years of age. We have previously reported that Pneumovax administered to healthy 12-month-old Fijian infants elicits significant serotype-specific IgG responses. However, the functional capacity of these responses in 12-month-old infants is not known. Objective We sought to assess the functional, serotype-specific immune response of 12-month-old infants after immunization with Pneumovax. Methods Functional responses of 12-month-old infants were assessed by using the opsonophagocytic and antibody avidity assay against 8 serotypes and 23 serotypes, respectively. Results Seventy-one percent of infants produced strong opsonophagocytic activity against 4 of 8 serotypes, and 30% produced high-avidity serotype-specific IgG antibodies to 10 of 23 serotypes at 2 weeks after Pneumovax. Responses were protective for most serotypes that cause disease in Western countries, whereas responses to most of the epidemiologically relevant serotypes for developing countries were low. Conclusion This is the first comprehensive study evaluating the functional antibody response to Pneumovax in 12-month-old infants. Pneumovax induced functional antibody responses to several serotypes causing disease in Western countries but induced poorer responses to serotypes that are responsible for the majority of disease in developing countries. Pneumovax might be of benefit in some populations, but further studies are required before this can be recommended in developing countries.
Background The prevalence of school students at risk of anaphylaxis in Victoria is unknown and has not been previously studied. Similarly, rates of adrenaline autoinjector usage in the school ...environment have yet to be determined given increasing prescription rates. Objectives We sought to determine time trends in prevalence of school children at risk of anaphylaxis across all year levels and the annual usage rate of adrenaline autoinjectors in the school setting relative to the number of students at risk of anaphylaxis. Methods Statewide surveys from more than 1,500 government schools including more than 550,000 students were used and prevalence rates (%) with 95% CIs were calculated. Results The overall prevalence of students at risk of anaphylaxis has increased 41% from 0.98% (95% CI, 0.95-1.01) in 2009 to 1.38% (95% CI, 1.35-1.41) in 2014. There was a significant drop in reporting of anaphylaxis risk with transition from the final year of primary school to the first year of secondary school, suggesting a change in parental reporting of anaphylaxis risk among secondary school students. The number of adrenaline autoinjectors activated per 1000 students at risk of anaphylaxis ranged from 6 to 8 per year, with consistently higher activation use in secondary school students than in primary school students. Conclusions Statewide prevalence of anaphylaxis risk has increased in children attending Victorian government schools. However, adrenaline autoinjector activation has remained fairly stable despite known increase in the rates of prescription.
Heparan sulfate proteoglycans are an important and abundant component of the extracellular matrix, which undergo substantial remodeling throughout tumorigenesis via the enzymatic activity of ...heparanase. Heparanase has been shown to be upregulated in many human cancers; however, its specific functions in human pancreatic neuroendocrine tumors (PanNETs) and spontaneous mouse models of cancer have not been evaluated. Here, we investigated the role of heparanase in PanNETs using patient samples and the RIP1-Tag2 (RT2) PanNET-transgenic mouse model. High heparanase expression significantly correlated with more advanced tumor stage, higher tumor grade and the presence of distant metastasis in PanNET patients. We genetically manipulated heparanase levels in the RT2 model using heparanase-transgenic mice, which constitutively overexpress heparanase, and heparanase-knockout mice. Heparanase was found to have a critical role in promoting tumor invasion, through both macrophage and cancer cell sources in the tumor microenvironment. In addition, elevated heparanase levels significantly increased peritumoral lymphangiogenesis in vivo and promoted the trans-differentiation of macrophages into lymphatic endothelial cell-like structures in culture. Conversely, we found that heparanase deletion led to increased angiogenesis and pericyte coverage. Together, these data identify important roles for heparanase in regulating several critical aspects of tumorigenesis, demonstrating that heparanase represents a potential therapeutic target for PanNET patients.
Single-nucleotide polymorphism (SNP)-based genome-wide association study revealed that markers on chromosome 17q21 were linked to childhood asthma but not atopy in Caucasians, with the strongest ...signal being detected for the SNP rs7216389 in the ORMDL3 gene. Such association was unknown in Chinese. This study delineated the allele and genotype frequencies of 10 SNPs at chromosome 17q21, and investigated the relationship between these SNPs and asthma and plasma IgE in southern Chinese children. Asthmatic children and non-allergic controls were recruited from pediatric clinics. Their plasma total and aeroallergen-specific IgE concentrations were measured by immunoassay. Ten SNPs on 17q21 region were genotyped by multiplex SNaPshottrade mark sign, and their genotype associations with asthma traits analyzed using multivariate regression. 315 patients and 192 controls were enrolled. The allele frequency for C allele of rs7216389 varied significantly from 0.232 in our controls, 0.389 in Han Chinese to 0.536 in Caucasians. Asthma diagnosis was associated with rs11650680 and five other SNPs including rs7216389 (P = 0.019-0.034), whereas atopy was associated only with rs11650680 (P = 0.0004). Linear regression revealed the covariates for plasma total IgE to be significant for rs11650680 (P = 0.008-0.0002). Haplotypic associations were found with atopy and increased plasma total IgE, with the respective odds ratios and 95% confidence intervals for TTTCCGTT haplotype to be 0.21 and 0.09-0.52 (P = 0.0002) and 0.41 and 0.18-0.90 (P = 0.025). Childhood asthma and atopy are associated with chromosome 17q21 in Chinese, but such association may involve genes other than ORMDL3 in this region.
Objectives. Previous studies reported that overweight older adults had a lower mortality after cardiovascular diseases attack, indicating being thinner might not always be better. However, there is ...an ongoing debate about what is the optimal range of body mass index (BMI) for the aged population. We aimed to evaluate the value of BMI for the prediction of incident diabetes mellitus (DM) in the Chinese elderly population. Methods. A total number of 6,911 Chinese elderly people (4,110 men and 2,801 women, aged 71±6.0 years) were included in this cohort study. BMI was measured at baseline (Jan 1, 2014, to Dec 31, 2014). All the participants were further classified into six groups: <18.5 kg/m2, 18.5 to <22.5 kg/m2, 22.5 to <25.0 kg/m2, 25.0 to <27.5 kg/m2, 27.5 to <30.0 kg/m2, and ≥30.0 kg/m2. Fasting blood glucose (FBG) and glycated hemoglobin A1c (HbA1c) were annually measured during follow-up (Jan 1, 2015-May 31, 2019). DM was confirmed if either FBG≥7.0 mmol/L or HbA1c≥6.5%. We used the Cox proportional hazard regression model to evaluate the association between BMI and the prediction of incident DM. Results. Comparing individuals with a BMI range of 18.5 to <22.5 kg/m2 (reference), the hazard ratio for incident DM was 2.13 (95% CI: 1.54~2.95), 2.14 (95% CI: 1.53~3.00), 3.17 (95% CI: 2.19~4.59), 3.15 (95% CI: 1.94~5.09), and 3.14 (95% CI: 1.94~5.09) for the group with a BMI range of 22.5 to <25.0 kg/m2, 25.0 to <27.5 kg/m2, 27.5 to <30.0 kg/m2, and ≥30.0 kg/m2 after adjusting for baseline age, sex, blood pressure, lipid profiles, and eGFR (P trend < 0.001), after adjusting for the abovementioned confounders. The association tended to be closer in men and young participants, compared with their counterparts. Conclusions. High BMI was associated with a high risk of developing DM in the Chinese aged population. Thus, it is optimal for the aged population to maintain their body weight within a reasonable range to prevent chronic diseases.
A series of functionalized pentacene derivatives based on symmetric and asymmetric substitutions of the terminal rings are synthesized (see figure). Field‐effect mobilities as high as 0.23 cm2 V–1 ...s–1 are obtained with 2,3‐dibrompentacene. These devices show improved stability compared to pentacene and exhibit no significant decrease in mobility or on/off ratio when stored in air, with and without light exposure, even after three months.
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