Early-life exposure to humidifier disinfectant determines the prognosis of lung function in children

Background Use of humidifier disinfectants (HD) at home leads to chemical airborne exposure, causing HD associated lung injury (HDLI) with high mortality. However, the lung function in children diagnosed with HDLI is not well studied. We investigated the effect of HD exposure on lung function, prognosis, and exposure characteristics associated with the lung function phenotype in children. Methods Eighty-one children diagnosed with HDLI in a nationwide cohort were tested for spirometry and diffusing capacity of the lung for carbon monoxide (DLco) from July 2013 and followed up with at five time points over 2 years. The results were compared with 122 children without HD exposure as controls. Home investigation and questionnaire analysis were conducted to assess HD inhalation exposure. Results HDLI survivors mean percent of predicted forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and corrected DLco were significantly lower compared with the control group. On longitudinal assessment, FVC was within the normal range, but flattened, and spirometry showed a predominantly restrictive pattern. Corrected DLco did not normalize above 80% despite increasing age. The persistently low phenotype of lung function was associated with initial exposure age, especially less than 12 months of age. Higher density HD exposure during sleep and close distance between the bed and the humidifier were significantly associated with persistently low corrected DLco. Conclusions HD exposure affects prolonged decrement in lung function, especially DLco, particularly among children who are exposed within the first year of life. These results suggested that early-life HD exposure determines long-term prognosis of lung function in children.This study was supported by the Korea Ministry of Environment (MOE) as the Environmental Health Action Program (2016001360006), and the Environmental Health Center for Hazardous Chemical Exposure funded by Ministry of Environment Republic of Korea (2019). The funding sponsors had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results

A guanidine-appended scyllo-inositol derivative AAD-66 enhances brain delivery and ameliorates Alzheimer’s phenotypes

Alzheimer's disease (AD) is a degenerative brain disease that destroys memory and other important mental functions but lacks efficient therapeutic agents. Blocking toxic amyloid beta (A beta) could be beneficial for AD and represents a promising therapeutic strategy for AD treatment. scyllo-Inositol (SI) is a potential therapeutic for AD by directly interacting with the A beta peptide to inhibit A beta 42 fiber formation. Clinical studies of SI showed promising benefits on mild to moderate AD, however, with limitations on dosage regime. A new strategy to enhance the brain delivery of SI is needed to achieve the efficacy with minimum adverse effects. Herein, we report that a novel guanidine-appended SI derivative AAD-66 resulted in more effective reductions of brain A beta and plaque deposits, gliosis, and behavioral memory deficits in the disease-established 5xFAD mice. Overall, our present study reveals the potential of AAD-66 as a promising therapeutic agent for AD.111sciescopu

Age is a determinant factor in the susceptibility of domestic ducks to H5 clade 2.3.2.1c and 2.3.4.4e high pathogenicity avian influenza viruses

High pathogenicity avian influenza (HPAI) is a viral disease with devastating consequences for the poultry industry worldwide. Domestic ducks are a major source of HPAI viruses in many Eurasian countries. The infectivity and pathogenicity of HPAI viruses in ducks vary depending on host and viral factors. To assess the factors influencing the infectivity and pathogenicity of HPAI viruses in ducks, we compared the pathobiology of two HPAI viruses (H5N1 clade 2.3.2.1c and H5N6 clade 2.3.4.4e) in 5- and 25-week-old ducks. Both HPAI viruses caused mortality in a dose-dependent manner (104, 106, and 108 EID50) in young ducks. By contrast, adult ducks were infected but exhibited no mortality due to either virus. Viral excretion was higher in young ducks than in adults, regardless of the HPAI strain. These findings demonstrate the age-dependent mortality of clade 2.3.2.1c and clade 2.3.4.4e H5 HPAI viruses in ducks

Analysis of information diffusion for threshold models on arbitrary networks

Diffusion of information via networks has been extensively studied for decades. We study the general threshold model that embraces most of the existing models for information diffusion. In this paper, we first analyze diffusion processes under the linear threshold model, then generalize it into the general threshold model. We give a closed formula for estimating the final cascade size for those models and prove that the actual final cascade size is concentrated around the estimated value, for any network structure with node degrees ω(log n), where n is the number of nodes. Our analysis analytically explains the tipping point phenomenon that is commonly observed in information diffusion processes. Based on the formula, we devise an efficient algorithm for estimating the cascade size for general threshold models on any network with any given initial adopter set. Our algorithm can be employed as a subroutine for numerous algorithms for diffusion analysis such as influence maximization problem. Through experiments on real-world and synthetic networks, we confirm that the actual cascade size is very close to the value computed by our formula and by our algorithm, even when the degrees of the nodes are not so large

Phase transitions for information diffusion in random clustered networks

We study the conditions for the phase transitions of information diffusion in complex networks. Using the random clustered network model, a generalisation of the Chung-Lu random network model incorporating clustering, we examine the effect of clustering under the Susceptible-Infected-Recovered (SIR) epidemic diffusion model with heterogeneous contact rates. For this purpose, we exploit the branching process to analyse information diffusion in random unclustered networks with arbitrary contact rates, and provide novel iterative algorithms for estimating the conditions and sizes of global cascades, respectively. Showing that a random clustered network can be mapped into a factor graph, which is a locally tree-like structure, we successfully extend our analysis to random clustered networks with heterogeneous contact rates. We then identify the conditions for phase transitions of information diffusion using our method. Interestingly, for various contact rates, we prove that random clustered networks with higher clustering coefficients have strictly lower phase transition points for any given degree sequence. Finally, we confirm our analytical results with numerical simulations of both synthetically-generated and real-world networks

Management Requirements of Future Internet

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Towards Management of the Future Internet

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Risk Factors of Bone Mass Loss at the Lumbar Spine: A Longitudinal Study in Healthy Korean Pre- and Perimenopausal Women Older than 40 Years.

Longitudinal studies on bone mass decline for healthy women are sparse. We performed a retrospective longitudinal study to evaluate the factor associated with bone mass changes at the lumbar spine in healthy Korean pre- and perimenopausal women over the age of 40. We examined the relation of blood tests including thyroid function tests at baseline and follow-up to the annual percentage changes in average BMD of L2-L4 (A%ΔLSBMD). Four hundred and forty-three subjects without diseases or medications pertaining to bone metabolism were analyzed. The mean A%ΔLSBMD in these subjects was -0.45%/year. Though a significant correlation was observed between the A%ΔLSBMD and age, serum thyroid-stimulating hormone (TSH) level, total cholesterol (TC) level, low-density lipoprotein cholesterol (LDL-C) level, and estimated glomerular filtration rate (eGFR) at baseline and follow-up, there was a weak correlation between A%ΔLSBMD and these variables. From multiple linear regression analyses, the percent body fat, age, serum TSH level, serum uric acid level, and the menopause at follow-up were showed to have a significant association with the A%ΔLSBMD. Unlike age, percent body fat, and menopause at follow-up, which had a negative association with the A%ΔLSBMD, serum TSH level and serum uric acid level, had a positive association with the A%ΔLSBMD. The results from our study showed that the notable risk factors of BMD loss at the lumbar spine in population of our study were advancing age, menopause, higher percent body fat, lower normal TSH, and lower serum uric acid levels