Relative Role of Age Groups and Indoor Environments in Influenza Transmission Under Different Urbanization Rates in China.

Exploring the relative role of different indoor environments in respiratory infections transmission remains unclear, which is crucial for developing targeted nonpharmaceutical interventions. In this study, a total of 2,583,441 influenza-like illness cases tested from 2010 to 2017 in China were identified. An agent-based model was built and calibrated with the surveillance data, to assess the roles of 3 age groups (children <19 years, younger adults 19-60 years, older adults >60 years) and 4 types of indoor environments (home, schools, workplaces, and community areas) in influenza transmission by province with varying urbanization rates. When the urbanization rates increased from 35% to 90%, the proportion of children aged <19 years among influenza cases decreased from 76% to 45%. Additionally, we estimated that infections originating from children decreased from 95.1% (95% confidence interval (CI): 92.7, 97.5) to 59.3% (95% CI: 49.8, 68.7). Influenza transmission in schools decreased from 80.4% (95% CI: 76.5, 84.3) to 36.6% (95% CI: 20.6, 52.5), while transmission in the community increased from 2.4% (95% CI: 1.9, 2.8) to 45.4% (95% CI: 35.9, 54.8). With increasing urbanization rates, community areas and younger adults contributed more to infection transmission. These findings could help the development of targeted public health policies. This article is part of a Special Collection on Environmental Epidemiology. This article is part of a Special Collection on Environmental Epidemiology.

In vivo characterization of glycogen storage disease type III in a mouse model using glycoNOE MRI.

PURPOSE: Glycogen storage disease type III (GSD III) is a rare inherited metabolic disease characterized by excessive accumulation of glycogen in liver, skeletal muscle, and heart. Currently, there are no widely available noninvasive methods to assess tissue glycogen levels and disease load. Here, we use glycogen nuclear Overhauser effect (glycoNOE) MRI to quantify hepatic glycogen levels in a mouse model of GSD III. METHODS: Agl knockout mice (n = 13) and wild-type controls (n = 10) were scanned for liver glycogen content using glycoNOE MRI. All mice were fasted for 12 to 16 h before MRI scans. GlycoNOE signal was quantified by fitting the Z-spectrum using a four-pool Voigt lineshape model. Next, the fitted direct water saturation pool was removed and glycoNOE signal was estimated from the integral of the residual Z spectrum within -0.6 to -1.4 ppm. Glycogen concentration was also measured ex vivo using a biochemical assay. RESULTS: GlycoNOE MRI clearly distinguished Agl knockout mice from wild-type controls, showing a statistically significant difference in glycoNOE signals in the livers across genotypes. There was a linear correlation between glycoNOE signal and glycogen concentration determined by the biochemical assay. The obtained glycoNOE maps of mouse livers also showed higher glycogen levels in Agl knockout mice compared to wild-type mice. CONCLUSION: GlycoNOE MRI was used successfully as a noninvasive method to detect liver glycogen levels in mice, suggesting the potential of this method to be applied to assess glycogen storage diseases.

Creatine mapping of the brain at 3T by CEST MRI.

PURPOSE: To assess the feasibility of CEST-based creatine (Cr) mapping in brain at 3T using the guanidino (Guan) proton resonance. METHODS: Wild type and knockout mice with guanidinoacetate N-methyltransferase deficiency and low Cr and phosphocreatine (PCr) concentrations in the brain were used to assign the Cr and protein-based arginine contributions to the GuanCEST signal at 2.0 ppm. To quantify the Cr proton exchange rate, two-step Bloch-McConnell fitting was used to fit the extracted CrCEST line-shape and multi-B1 Z-spectral data. The pH response of GuanCEST was simulated to demonstrate its potential for pH mapping. RESULTS: Brain Z-spectra of wild type and guanidinoacetate N-methyltransferase deficiency mice show a clear Guan proton peak at 2.0 ppm at 3T. The CrCEST signal contributes ∼23% to the GuanCEST signal at B1 = 0.8 µT, where a maximum CrCEST effect of 0.007 was detected. An exchange rate range of 200-300 s-1 was estimated for the Cr Guan protons. As revealed by the simulation, an elevated GuanCEST in the brain is observed when B1 is less than 0.4 µT at 3T, when intracellular pH reduces by 0.2. Conversely, the GuanCEST decreases when B1 is greater than 0.4 µT with the same pH drop. CONCLUSIONS: CrCEST mapping is possible at 3T, which has potential for detecting intracellular pH and Cr concentration in brain.

The impact of isoflurane anesthesia on brain metabolism in mice: An MRI and electroencephalography study.

Isoflurane is one of the most widely used anesthetic agents in rodent imaging studies. However, the impact of isoflurane on brain metabolism has not been fully characterized to date, primarily due to a scarcity of noninvasive technologies to quantitatively measure the brain's metabolic rate in vivo. In this study, using noncontrast MRI techniques, we dynamically measured cerebral metabolic rate of oxygen (CMRO2) under varying doses of isoflurane anesthesia in mice. Concurrently, systemic parameters of heart and respiration rates were recorded alongside CMRO2. Additionally, electroencephalogram (EEG) recording was used to identify changes in neuronal activities under the same anesthetic regimen employed in the MRI experiments. We found suppression of the CMRO2 by isoflurane in a dose-dependent manner, concomitant with a diminished high-frequency EEG activity. The degree of metabolic suppression by isoflurane was strongly correlated with the respiration rate, which offers a potential approach to calibrate CMRO2 measurements. Furthermore, the metabolic level associated with neural responses of the somatosensory and motor cortices in mice was estimated as 308.2 µmol/100 g/min. These findings may facilitate the integration of metabolic parameters into future studies involving animal disease models and anesthesia usage.

The Association of Epicardial Adipose Tissue Volume and Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy: As Assessed by Cardiac MR.

BACKGROUND: Epicardial adipose tissue (EAT) is a metabolically active visceral fat linked to cardiovascular disease. Prior studies demonstrated the predictive value of EAT volume (EATV) in atrial fibrillation (AF) among hypertrophic obstructive cardiomyopathy patients. PURPOSE: To investigate the association between EATV and AF in hypertrophic cardiomyopathy (HCM). STUDY TYPE: Retrospective. POPULATION: Two hundred and twenty-four HCM patients (including 79 patients with AF and 145 patients without AF, 154 men) and 80 healthy controls (54 men). FIELD STRENGTH/SEQUENCE: 3.0 T scanner; balanced steady-state free precession (SSFP) cine sequence, gradient echo. ASSESSMENT: EAT thickness was assessed in the 4-chamber and basal short-axis planes. EAT volume was calculated by outlining the epicardial border and visceral pericardium layer on short-axis cine images. STATISTICAL TESTS: Shapiro-Wilk test, Student's t test or the Mann-Whitney U test, chi-square test or Fisher's exact test, Multivariate linear regression analyses, Multivariable binary logistic regression analysis. Intraclass correlation coefficient. Significance was determined at P < 0.05. RESULTS: EATV and EAT volume index (EATVI) were significantly greater in HCM patients with AF than those without AF (126.6 ± 25.9 mL vs. 90.5 ± 24.5 mL, and 73.0 ± 15.9 mL/m2 vs. 51.3 ± 13.4 mL/m2). EATVI was associated with AF in multivariable linear regression analysis among HCM patients (ß = 0.62). Multivariable logistic regression analysis revealed that compared to other indicators, the area under curve (AUC) of EATVI was 0.86 (cut-off, 53.9 mL/m2, 95% CI, 0.80-0.89), provided a better performance, with the sensitivity of 96.2% and specificity of 58.6%. The combined model exhibited superior association with AF presence compared to the clinical model (AUC 0.96 vs. 0.76) and the imaging model (AUC 0.96 vs. 0.93). DATA CONCLUSION: EATVI was associated with AF. EATVI was significantly correlated with incident AF, and provided a better performance in HCM patients compared to other indicators. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Online LC-Orbitrap MS method for the rapid molecular characterization of dissolved organic matter.

RATIONALE: High-resolution mass spectrometry (HRMS) combined with electrospray ionization (ESI) has been the most useful technique for molecular characterization of dissolved organic matter (DOM) derived from diverse sources. However, the comprehensive detection of DOM composition was hindered by ionization suppression observed in ESI sources. HRMS coupled with liquid chromatography (LC) is a potential tool for comprehensive molecular characterization of DOM. METHODS: The Suwannee River fulvic acids (SRFAs) and two DOM samples from seawater and refinery wastewater extracted by solid phase extraction (SPE) were analyzed by LC-Orbitrap MS coupled with ESI. The mobile phases, solvent composition, and gradient in the LC-Orbitrap MS analysis were optimized. RESULTS: The number of detected molecular formulae of SRFAs by online LC-Orbitrap MS was significantly increased by approximately 40% compared to direct injection. These additional detected compounds are mainly protein and lignin-like compounds, with a low O/C ratio and high H/C ratio. For the SRFAs, the relative standard deviations (%) of reproducibility are 5.51, 2.33, 7.97, and 1.80 for average O/C, H/C, double bond equivalent, and modified aromaticity index, respectively. CONCLUSIONS: This study proposed a simple and rapid method based on LC-Orbitrap MS for an in-depth analysis of the molecular composition of DOM, achieving a remarkable analysis time of only 5 min per sample. The rapid method provides a dependable and efficient approach for the molecular characterization of DOM, thereby advancing our comprehension and investigation of DOM across diverse ecosystems.

Revealing the backbone structures of land-based fulvic acids derived from river and soil through n-butylsilane reduction.

While ultra-high-resolution mass spectrometry has enabled the identification of the molecular composition of dissolved organic matter (DOM), elucidating its molecular structure remains a challenging endeavor. Here, two fulvic acids (FAs), one from river and the other from forest soil, were subjected to reduction using an optimized n-butylsilane (n-BS) reduction method. The reduction products were purified through a combination of liquid-liquid extraction and silica gel column chromatography, resulting in the separation into saturates, aromatics, and polar products. The polar products were analyzed by high-resolution mass spectrometry (HRMS), and the saturates and aromatics were analyzed using gas chromatography-mass spectrometry (GC-MS). HRMS results showed that the number of oxygen atoms and double-bond equivalent (DBE) values of FA decreased after reduction. GC-MS results revealed that a total of 270 hydrocarbon monomers were identified from the reduction products of a single sample, with the highest carbon number of cycloalkanes reaching C33. For the first time, steranes and hopanes were detected in the reduction products, potentially serving as evidence for the existence of carboxyl-rich alicyclic molecule (CRAM) precursors. Additionally, a significant number of polycyclic aromatic hydrocarbons were identified, and the potential sources of various compounds were preliminarily inferred based on their isomers. This study extends the knowledge of the possible backbone structure of the DOM and provides a new potential tool for investigating the origin and transformation mechanisms of DOM.

Influence of Double-Pulse Electrodeposition Parameters on the Performance of Ag/AgCl Electrochemical Electrode for Marine Electric Field.

This paper describes a Ag/AgCl electrochemical electrode for marine electric field measurements, which was prepared by depositing silver chloride on a silver foil substrate using double-pulse electrodeposition. The impact of positive direction peak current density and deposition time on electrode performance in the preparation of Ag/AgCl electrodes through double-pulse electrodeposition was investigated. Scanning electron microscopy and voltammetry have been used to study the properties of the prepared electrodes. This work reveals the correlation between the electrochemical behavior of electrodes and the physical properties of their surfaces, especially specific surface area and porosity. The study verified the characteristics of Ag/AgCl marine electric field electrodes obtained with different pulse parameters by analyzing the potential stability and noise level of the electrode in salt water. The study's results have positive significance for improving the accuracy of marine electric field measurements.

Coronavirus Disease 2019 and Airborne Transmission: Science Rejected, Lives Lost. Can Society Do Better?

This is an account that should be heard of an important struggle: the struggle of a large group of experts who came together at the beginning of the COVID-19 pandemic to warn the world about the risk of airborne transmission and the consequences of ignoring it. We alerted the World Health Organization about the potential significance of the airborne transmission of SARS-CoV-2 and the urgent need to control it, but our concerns were dismissed. Here we describe how this happened and the consequences. We hope that by reporting this story we can raise awareness of the importance of interdisciplinary collaboration and the need to be open to new evidence, and to prevent it from happening again. Acknowledgement of an issue, and the emergence of new evidence related to it, is the first necessary step towards finding effective mitigation solutions.

Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins.

Blood-brain barrier (BBB) plays a critical role in protecting the brain from toxins and pathogens. However, in vivo tools to assess BBB permeability are scarce and often require the use of exogenous contrast agents. In this study, we aimed to develop a non-contrast arterial-spin-labeling (ASL) based MRI technique to estimate BBB permeability to water in mice. By determining the relative fraction of labeled water spins that were exchanged into the brain tissue as opposed to those that remained in the cerebral veins, we estimated indices of global BBB permeability to water including water extraction fraction (E) and permeability surface-area product (PS). First, using multiple post-labeling delay ASL experiments, we estimated the bolus arrival time (BAT) of the labeled spins to reach the great vein of Galen (VG) to be 691.2 ± 14.5 ms (N = 5). Next, we investigated the dependence of the VG ASL signal on labeling duration and identified an optimal imaging protocol with a labeling duration of 1200 ms and a PLD of 100 ms. Quantitative E and PS values in wild-type mice were found to be 59.9 ± 3.2% and 260.9 ± 18.9 ml/100 g/min, respectively. In contrast, mice with Huntington's disease (HD) revealed a significantly higher E (69.7 ± 2.4%, P = 0.026) and PS (318.1 ± 17.1 ml/100 g/min, P = 0.040), suggesting BBB breakdown in this mouse model. Reproducibility studies revealed a coefficient-of-variation (CoV) of 4.9 ± 1.7% and 6.1 ± 1.2% for E and PS, respectively. The proposed method may open new avenues for preclinical research on pathophysiological mechanisms of brain diseases and therapeutic trials in animal models.

Guanidinium and amide CEST mapping of human brain by high spectral resolution CEST at 3 T.

PURPOSE: To extract guanidinium (Guan) and amide CEST on the human brain at 3 T MRI with the high spectral resolution (HSR) CEST combined with the polynomial Lorentzian line-shape fitting (PLOF). METHODS: Continuous wave (cw) turbo spin-echo (TSE) CEST was implemented to obtain the optimum saturation parameters. Both Guan and amide CEST peaks were extracted and quantified using the PLOF method. The NMR spectra on the egg white phantoms were acquired to reveal the fitting range and the contributions to the amide and GuanCEST. Two types of CEST approaches, including cw gradient- and spin-echo (cwGRASE) and steady state EPI (ssEPI), were implemented to acquire multi-slice HSR-CEST. RESULTS: GuanCEST can be extracted with the PLOF method at 3 T, and the optimum B 1 = 0.6 µ T $$ {\mathrm{B}}_1=0.6\kern0.2em \upmu \mathrm{T} $$ was determined for GuanCEST in white matter (WM) and 1.0 µT in gray matter (GM). The optimum B1  = 0.8-1 µT was found for amideCEST. AmideCEST is lower in both WM and GM collected with ssEPI compared to those by cwGRASE (ssEPI = [1.27-1.63]%; cwGRASE = [2.19-2.25]%). The coefficients of variation (COV) of the amide and Guan CEST in both WM and GM for ssEPI (COV: 28.6-33.4%) are significantly higher than those of cwGRASE (COV: 8.6-18.8%). Completely different WM/GM contrasts for Guan and amide CEST were observed between ssEPI and cwGRASE. The amideCEST was found to have originated from the unstructured amide protons as suggested by the NMR spectrum of the unfolded proteins in egg white. CONCLUSION: Guan and amide CEST mapping can be achieved by the HSR-CEST at 3 T combing with the PLOF method.

The exchange rate of creatine CEST in mouse brain.

PURPOSE: To estimate the exchange rate of creatine (Cr) CEST and to evaluate the pH sensitivity of guanidinium (Guan) CEST in the mouse brain. METHODS: Polynomial and Lorentzian line-shape fitting (PLOF) were implemented to extract the amine, amide, and Guan CEST signals from the brain Z-spectrum at 11.7T. Wild-type (WT) and knockout mice with the guanidinoacetate N-methyltransferase deficiency (GAMT-/- ) that have low Cr and phosphocreatine (PCr) concentrations in the brain were used to extract the CrCEST signal. To quantify the CrCEST exchange rate, a two-step Bloch-McConnell (BM) fitting was used to fit the CrCEST line-shape, B1 -dependent CrCEST, and the pH response with different B1 values. The pH in the brain cells was altered by hypercapnia to measure the pH sensitivity of GuanCEST. RESULTS: Comparison between the Z-spectra of WT and GAMT-/- mice suggest that the CrCEST is between 20% and 25% of the GuanCEST in the Z-spectrum at 1.95 ppm between B1 = 0.8 and 2 µT. The CrCEST exchange rate was found to be around 240-480 s-1 in the mouse brain, which is significantly lower than that in solutions (∼1000 s-1 ). The hypercapnia study on the mouse brain revealed that CrCEST at B1 = 2 µT and amineCEST at B1 = 0.8 µT are highly sensitive to pH change in the WT mouse brain. CONCLUSIONS: The in vivo CrCEST exchange rate is slow, and the acquisition parameters for the CrCEST should be adjusted accordingly. CrCEST is the major contribution to the opposite pH-dependence of GuanCEST signal under different conditions of B1 in the brain.

Bloch simulator-driven deep recurrent neural network for magnetization transfer contrast MR fingerprinting and CEST imaging.

PURPOSE: To develop a unified deep-learning framework by combining an ultrafast Bloch simulator and a semisolid macromolecular magnetization transfer contrast (MTC) MR fingerprinting (MRF) reconstruction for estimation of MTC effects. METHODS: The Bloch simulator and MRF reconstruction architectures were designed with recurrent neural networks and convolutional neural networks, evaluated with numerical phantoms with known ground truths and cross-linked bovine serum albumin phantoms, and demonstrated in the brain of healthy volunteers at 3 T. In addition, the inherent magnetization-transfer ratio asymmetry effect was evaluated in MTC-MRF, CEST, and relayed nuclear Overhauser enhancement imaging. A test-retest study was performed to evaluate the repeatability of MTC parameters, CEST, and relayed nuclear Overhauser enhancement signals estimated by the unified deep-learning framework. RESULTS: Compared with a conventional Bloch simulation, the deep Bloch simulator for generation of the MTC-MRF dictionary or a training data set reduced the computation time by 181-fold, without compromising MRF profile accuracy. The recurrent neural network-based MRF reconstruction outperformed existing methods in terms of reconstruction accuracy and noise robustness. Using the proposed MTC-MRF framework for tissue-parameter quantification, the test-retest study showed a high degree of repeatability in which the coefficients of variance were less than 7% for all tissue parameters. CONCLUSION: Bloch simulator-driven, deep-learning MTC-MRF can provide robust and repeatable multiple-tissue parameter quantification in a clinically feasible scan time on a 3T scanner.

Noninvasive assessment of renal dynamics and pH in a unilateral ureter obstruction model using DCE MR-CEST urography.

PURPOSE: To assess the potential of DCE MR CEST urography for assessing renal function in mice with unilateral ureter obstruction (UUO) by simultaneous pH and renal uptake/clearance measurements following injection of iopamidol. METHODS: The right ureter of nine mice was obstructed via suture ligation. The animals were imaged at day 1, 2, and 3 post-obstruction on an 11.7T MRI scanner. Ninety-six sets of saturated CEST images at 4.3 and 5.5 ppm were collected. Renal pH values were obtained by calculating the signal ratio for these two frequencies and using a pH calibration curve. Renal time activity curves were measured as a percentage change in the post-injection CEST signal at 4.3 ppm relative to the average pre-injection signal. RESULTS: For the healthy mice, the time activity curves of both kidneys were nearly identical and displayed rapid excretion of contrast. For the UUO mice, the dynamic CEST curves for the obstructed kidneys displayed prolonged time to peak (TTP) values and delayed contrast excretion compared with the contralateral (CL) kidneys. Renal pH maps of the healthy animals showed similar acidic values for both kidneys (pH 6.65 ± 0.04 vs 6.67 ± 0.02), whereas in the obstructed kidneys there was a significant increase in pH values compared with the CL kidneys (pH 6.67 ± 0.08 vs 6.79 ± 0.11 in CL and UUO kidneys, respectively). CONCLUSION: Our findings indicate that DCE-MR-CEST urography can detect changes in renal uptake/excretion and pH homeostasis and distinguish between obstructed and unobstructed kidney as early as 1 day after UUO.

Normal Values of Magnetic Resonance T1ρ Relaxation Times in the Adult Heart at 1.5 T MRI.

BACKGROUND: T1ρ mapping is a new quantitative MRI technique in recent years. In order to use T1ρ mapping as a noncontrast method to assess myocardial fibrosis, it is necessary to establish a range of normal values. PURPOSE: To establish a potential normal range of cardiac T1ρ values in healthy adults and to explore the influence of slice location and gender on T1ρ values. STUDY TYPE: Prospective. POPULATION: A total of 57 healthy volunteers without cardiovascular risk factors (age 26.7 ± 11.8 years; 29 males). FIELD STRENGTH/SEQUENCE: 1.5 T; modified Look-Locker inversion recovery (MOLLI) (T1 mapping), multiecho gradient-spin-echo (GraSE) (T2 mapping) and T1ρ -prepared steady-state free precession (T1ρ mapping) sequences. ASSESSMENT: Basal, mid, and apical short-axis left ventricular T1 , T2 , and T1ρ maps were acquired. T1ρ maps at spin-locking frequencies of 5 and 400 Hz were subtracted to create myocardial fibrosis index (mFI) maps. Slice-average and global average T1 , T2 , T1ρ , and mFI values were determined. STATISTICAL TESTS: Shapiro-Wilk test, Independent t-test, ANOVA test, Pearson correlation coefficient (r). SIGNIFICANCE: P value < 0.05. RESULTS: The global average values of T1 , T2 , T1ρ, and mFI were 1053 ± 34 msec, 51.9 ± 2.3 msec, 47.9 ± 2.8 msec, and 4.4 ± 1.6 msec. T1ρ values showed a significant gradual increase from the basal slice to the apical slice of the heart (basal 46.5 ± 2.7 msec, mid 48.0 ± 2.9 msec, apical 49.2 ± 3.3 msec). The T1ρ and mFI values of females (49.7 ± 2.4 msec and 5.1 ± 1.2 msec, respectively) were significantly higher than those of males (46.2 ± 1.9 msec and 3.7 ± 1.7 msec, respectively). In addition, there was a moderate positive correlation between global T1ρ values and global T1 values (r = 0.44, P < 0.05) and a moderate positive correlation between global T1ρ values and global T2 values (r = 0.42, P < 0.05). DATA CONCLUSION: In this study, the global T1ρ values of healthy adults' hearts were 47.9 ± 2.8 msec. This study found that gender and slice location of myocardium can affect the T1ρ values. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

Comparative analysis of inflight transmission of SARS-CoV-2, influenza, and SARS-CoV-1.

The aim of this study is to evaluate the infection risk of aircraft passengers seated within and beyond two rows of the index case(s) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A(H1N1)pdm09 virus, and SARS-CoV-1. PubMed databases were searched for articles containing information on air travel-related transmission of SARS-CoV-2, influenza A(H1N1)pdm09 virus, and SARS-CoV-1 infections. We performed a meta-analysis of inflight infection data. In the eight flights where the attack rate could be calculated, the inflight SARS-CoV-2 attack rates ranged from 2.6% to 16.1%. The risk ratios of infection for passengers seated within and outside the two rows of the index cases were 5.64 (95% confidence interval (CI):1.94-16.40) in SARS-CoV-2 outbreaks, 4.26 (95% CI:1.08-16.81) in the influenza A(H1N1)pdm09 virus outbreaks, and 1.91 (95% CI:0.80-4.55) in SARS-CoV-1 outbreaks. Furthermore, we found no significant difference between the attack rates of SARS-CoV-2 in flights where the passengers were wearing masks and those where they were not (p = 0.22). The spatial distribution of inflight SARS-CoV-2 outbreaks was more similar to that of the influenza A(H1N1)pdm09 virus outbreaks than to that of SARS-CoV-1. Given the high proportion of asymptomatic or pre-symptomatic infection in SARS-CoV-2 transmission, we hypothesised that the proximity transmission, especially short-range airborne route, might play an important role in the inflight SARS-CoV-2 transmission.

Early-life exposure to air pollution associated with food allergy in children: Implications for 'one allergy' concept.

BACKGROUND: The rapid increase of food allergy (FA) has become the "second wave" of allergy epidemic and is now a major global public health concern. Mounting evidence indicates that early life exposure to air pollution is associated with the "first wave" of allergy epidemic (including asthma, allergic rhinitis and eczema) in children, but little is known about its association with FA. OBJECTIVES: We hypothesize FA has triple exposure pathways, gut-skin-airway, and investigate the effects of airway exposure to outdoor and indoor air pollution on childhood FA. METHODS: A cohort study of 2598 preschool children aged 3-6 years old was conducted in Changsha, China. The prevalence of FA was surveyed using a standard questionnaire by International Study of Asthma and Allergies in Childhood (ISAAC). Exposure to indoor air pollution was assessed by four indicators: new furniture, redecoration, mold or dampness, and window condensation. Exposure to outdoor air pollution was evaluated by the concentrations of PM10, SO2 and NO2, which were obtained from the monitored stations. Both prenatal and postnatal exposure windows were considered. The association between exposure to outdoor/indoor air pollution and childhood FA was estimated by multiple logistic regression models using odds ratio (OR) and a 95% confidence interval (CI). RESULTS: A total of 14.9% children reported FA. The prevalence was significantly associated with exposure to indoor air pollution, OR (95% CI) = 1.93 (1.35-2.75) for prenatal exposure to mold/dampness and 1.49 (1.07-2.10) and 1.41 (1.04-1.89) respectively for postnatal exposure to new furniture and window condensation. The prevalence of FA was also associated with prenatal and postnatal exposure to outdoor air pollution, particularly the traffic-related air pollutant NO2, with adjusted ORs (95% Cls) respectively 1.24 (1.00-1.54) and 1.38 (1.03-1.85) per interquartile range (IQR) increase. Sensitivity analysis showed that the association between outdoor/indoor air pollution and childhood FA was significant only in young children aged 3-4 years. CONCLUSION: Early-life exposure to high levels of outdoor and indoor air pollution in China due to the rapid economic growth and fast urbanization in the past decades may contribute to the rapid increase of food allergy (FA) in children. Our study indicates that, in addition to gut and skin, airway may be a new route of food sensitization. Air pollution leads to the first and second waves of allergy epidemics, suggesting a concept of 'one allergy' disease.

Magnetic resonance imaging of glycogen using its magnetic coupling with water.

Glycogen plays a central role in glucose homeostasis and is abundant in several types of tissue. We report an MRI method for imaging glycogen noninvasively with enhanced detection sensitivity and high specificity, using the magnetic coupling between glycogen and water protons through the nuclear Overhauser enhancement (NOE). We show in vitro that the glycogen NOE (glycoNOE) signal is correlated linearly with glycogen concentration, while pH and temperature have little effect on its intensity. For validation, we imaged glycoNOE signal changes in mouse liver, both before and after fasting and during glucagon infusion. The glycoNOE signal was reduced by 88 ± 16% (n = 5) after 24 h of fasting and by 76 ± 22% (n = 5) at 1 h after intraperitoneal (i.p.) injection of glucagon, which is known to rapidly deplete hepatic glycogen. The ability to noninvasively image glycogen should allow assessment of diseases in which glucose metabolism or storage is altered, for instance, diabetes, cardiac disease, muscular disorders, cancer, and glycogen storage diseases.

Age-dependent cerebrospinal fluid-tissue water exchange detected by magnetization transfer indirect spin labeling MRI.

PURPOSE: A non-invasive magnetization transfer indirect spin labeling (MISL) MRI method is developed to quantify the water exchange between cerebrospinal fluid (CSF) and other tissues in the brain and to examine the age-dependence of water exchange. METHOD: In the pulsed MISL, we implemented a short selective pulse followed by a post-labeling delay before an MRI acquisition with a long echo time; in the continuous MISL, a train of saturation pulses was applied. MISL signal (∆Z) was obtained by the subtraction of the label MRI at -3.5 ppm from the control MRI at 200 ppm. CSF was extracted from the mouse ventricles for the MISL optimization and validation. Comparison between wild type (WT) and aquaporin-4 knockout (AQP4-/- ) mice was performed to examine the contributions of CSF water exchange, whereas its age-dependence was investigated by comparing the adult and young WT mice. RESULTS: The pulsed MISL method observed that the MISL signal reached the maximum at 1.5 s. The continuous MISL method showed the highest MISL signal in the fourth ventricle (∆Z = 13.5% ± 1.4%), whereas the third ventricle and the lateral ventricles had similar MISL ∆Z values (∆Z = 12.0% ± 1.8%). Additionally, significantly lower ∆Z (9.3%-18.7% reduction) was found in all ventricles for the adult mice than those of the young mice (p < 0.02). For the AQP4-/- mice, the ∆Z values were 5.9%-8.3% smaller than those of the age-matched WT mice in the lateral and fourth ventricles, but were not significant. CONCLUSION: The MISL method has a great potential to study CSF water exchange with the surrounding tissues in brain.

Quantitative cerebrovascular reactivity MRI in mice using acetazolamide challenge.

PURPOSE: To develop a quantitative MRI method to estimate cerebrovascular reactivity (CVR) in mice. METHODS: We described an MRI procedure to measure cerebral vasodilatory response to acetazolamide (ACZ), a vasoactive agent previously used in human clinical imaging. Vascular response was determined by cerebral blood flow (CBF) measured with phase-contrast or pseudo-continuous arterial spin labeling MRI. Vasodilatory input intensity was determined by plasma ACZ level using high-performance liquid chromatography. We verified the source of the CVR MRI signal by comparing ACZ injection to phosphate-buffered saline injection and noninjection experiments. Dose dependence and feasibility of regional CVR measurement were also investigated. RESULTS: Cerebral blood flow revealed an exponential increase following intravenous ACZ injection, with a time constant of 1.62 min. In contrast, phosphate-buffered saline or noninjection exhibited a slow linear CBF increase, consistent with a gradual accumulation of anesthetic agent, isoflurane, used in this study. When comparing different ACZ doses, injections of 30, 60, 120, and 180 mg/kg yielded a linear increase in plasma ACZ concentration (p < 0.0001). On the other hand, CBF changes under these doses were not different from each other (p = 0.50). The pseudo-continuous arterial spin labeling MRI with multiple postlabeling delays revealed similar vascular responses at different postlabeling delay values. There was a regional difference in CVR (p = 0.005), with isocortex (0.81 ± 0.17%/[µg/ml]) showing higher CVR than deep-brain regions. Mice receiving multiple ACZ injections lived for a minimum of 6 months after the study without noticeable aberrant behavior or appearance. CONCLUSIONS: We demonstrated the proof-of-principle of a new quantitative CVR mapping technique in mice.