Intranasal administration of ceramide liposome suppresses allergic rhinitis by targeting CD300f in murine models.

Allergic rhinitis (AR) is caused by type I hypersensitivity reaction in the nasal tissues. The interaction between CD300f and its ligand ceramide suppresses immunoglobulin E (IgE)-mediated mast cell activation. However, whether CD300f inhibits the development of allergic rhinitis (AR) remains elusive. We aimed to investigate the roles of CD300f in the development of AR and the effectiveness of intranasal administration of ceramide liposomes on AR in murine models. We used ragweed pollen-induced AR models in mice. Notably, CD300f deficiency did not significantly influence the ragweed-specific IgE production, but increased the frequency of mast cell-dependent sneezing as well as the numbers of degranulated mast cells and eosinophils in the nasal tissues in our models. Similar results were also obtained for MCPT5-exprssing mast cell-specific loss of CD300f. Importantly, intranasal administration of ceramide liposomes reduced the frequency of sneezing as well as the numbers of degranulated mast cells and eosinophils in the nasal tissues in AR models. Thus, CD300f-ceramide interaction, predominantly in mast cells, alleviates the symptoms and progression of AR. Therefore, intranasal administration of ceramide liposomes may be a promising therapeutic approach against AR by targeting CD300f.

Urinary neonicotinoids and metabolites are associated with obesity risk in Chinese school children.

BACKGROUND: Neonicotinoids are the most widely used insecticides. Laboratory studies have suggested that neonicotinoids are one potential obesogen, but relevant data are limited in human. OBJECTIVE: To examine the association between exposure to neonicotinoids and childhood obesity. METHODS: We investigated 442 children in Shanghai, East China and measured eight neonicotinoids (thiamethoxam, clothianidin, acetamiprid, imidacloprid, thiacloprid, nitenpyram, dinotefuran, and imidaclothiz) and four metabolites (N-desmethyl-thiamethoxam, N-desmethyl-clothianidin, N-desmethyl-acetamiprid, and 5-OH-imidacloprid) in urine. Body mass index (BMI) and waist circumference (WC) were used to identify general overweight/obesity and central obesity, respectively. Linear and logistic regression models based on generalized estimating equations were used to investigate the associations of urinary neonicotinoids and metabolites with BMI z-score, WC z-score, general overweight/obesity, and central obesity. RESULTS: Children with a positive detection of clothianidin and its metabolite had a marginally higher BMI z-score (regression coefficient (ß): 0.08, 95% confidence interval (95% CI): 0.01, 0.14) after adjusted for relevant covariates. After creatinine-adjusted concentration was trichotomized, compared to children with a negative detection, children in the high urinary concentration of acetamiprid and its metabolite had a low BMI z-score (ß: -0.19, 95%CI: -0.30, -0.08), children in the medium urinary concentration of neonicotinoids and metabolites other than thiamethoxam, clothianidin, acetamiprid, and their metabolites had a marginally higher BMI z-score (ß: 0.25, 95%CI: 0.03, 0.46), a higher WC z-score (ß: 0.24, 95%CI: 0.14, 0.33), and a higher odds of central obesity (odds ratio (OR): 2.16, 95% CI: 1.28, 3.63), and children in the medium urinary concentration of all neonicotinoids and metabolites had a higher odds of central obesity (OR: 1.55, 95%CI: 1.04, 2.33). Some associations showed sex- and age- related differences. CONCLUSION: Urinary neonicotinoids and metabolites were found to be differently associated with obesity-related indexes, which suggested that exposure to neonicotinoids might have a mixed effect on childhood obesity.

Source and health risk of urinary neonicotinoids in Tibetan pregnant women.

High altitude could influence the level of exposure to neonicotinoids, but relevant data remain limited for people living in Tibet. We investigated 476 Tibetan pregnant women from Lhasa of Tibet, China in 2021 and measured eight neonicotinoids and four metabolites in urine. Food consumption was investigated by a food frequency questionnaire. Health risk was assessed by using hazard quotient (HQ) and hazard index (HI) based on acceptable daily dose or chronic reference dose. Neonicotinoids and metabolites were overall detected in 56.5% of urine samples with a median concentration being 0.73 µg g-1 creatinine. Four neonicotinoids or metabolites were detected in more than 10% of urine samples, including N-desmethyl-acetamiprid (47.5%), clothianidin (15.5%), thiamethoxam (16.0%), and imidacloprid (10.5%). Annual household income, family smoking, and pre-pregnancy body mass index were associated with the detection frequencies of neonicotinoids. Pregnant women with a higher consumption frequency of wheat, rice, fresh vegetable, fresh fruit, beef and mutton, fresh milk, yoghourt, candy and chocolate, or carbonated drinks had a higher detection frequency of neonicotinoids. Both HQ and HI were less than one. There was an evident exposure to neonicotinoids in Tibetan pregnant women with both plant- and animal-derived food items as exposure sources, but a low health risk was found based on current safety thresholds.

Prevalence of antibiotic prescribing in COVID-19 patients in China and other low- and middle-income countries during the pandemic (December 2019-March 2021): a systematic review and meta-analysis.

OBJECTIVES: Low- and middle-income countries (LMICs) are particularly vulnerable to the threat of antimicrobial resistance (AMR). Use of antibiotics to treat COVID-19 patients during the pandemic may have contributed to increasing the AMR burden, but systematic evidence is lacking. METHODS: We searched Web of Science, EMBASE, PubMed, China National Knowledge Infrastructure (CNKI) and VIP databases from 1 December 2019 to 31 March 2021. Interventional and observation studies across all settings that reported antibiotic use in at least 10 COVID-19 patients were included. We restricted publications to English and Chinese languages. Screening and data extraction were undertaken by at least two independent reviewers. Results were synthesized using random-effects meta-analyses. Subgroup analyses and meta-regression were used to explore heterogeneities. This review was registered with PROSPERO (CRD42021288291). RESULTS: We included 284 studies involving 210 611 participants in 19 countries. The antibiotic prescribing rates (APRs) in COVID-19 inpatients were 71.7% (95% CI 66.7%-76.5%) in China and 86.5% (77.1%-93.9%) in other LMICs, respectively. APR was lower in mild/moderate cases in China [66.9% (57.9%-75.4%) compared with 91.8% (71.4%-100%) in other LMICs]. High APRs were found among pregnant women and the elderly in China. Disparities in APRs of other patient groups were identified. In studies reporting bacterial infections, the prevalence was 17.3% (10.0%-25.9%) in China and 24.9% (0.1%-68.8%) in other LMICs. Several antibiotics on the WHO 'Watch' and 'Reserve' lists were prescribed frequently in LMICs. CONCLUSIONS: Inappropriate antibiotic use and high prevalence of antibiotic prescribing were found in COVID-19 inpatients in many LMICs.

Murine model identifies tropomyosin as IgE cross-reactive protein between house dust mite and coho salmon that possibly contributes to the development of salmon allergy.

Background: Recently, we have developed a method to identify IgE cross-reactive allergens. However, the mechanism by which IgE cross-reactive allergens cause food allergy is not yet fully understood how. In this study, we aimed to understand the underlying pathogenesis by identifying food allergens that cross-react with house dust mite allergens in a murine model. Material and methods: Allergenic protein microarray analysis was conducted using serum from mice intraperitoneally injected with Dermatophagoides pteronyssinus (Der p) extract plus alum or alum alone as controls. Der p, Dermatophagoides farinae (Der f), coho salmon extract-sensitized and control mice were analyzed. Serum levels of IgE against Der p, Der f, coho salmon extract, protein fractions of coho salmon extract separated by ammonium sulfate precipitation and anion exchange chromatography, and recombinant coho salmon tropomyosin or actin were measured by an enzyme-linked immunosorbent assay. A murine model of cutaneous anaphylaxis or oral allergy syndrome (OAS) was established in Der p extract-sensitized mice stimulated with coho salmon extract, tropomyosin, or actin. Results: Protein microarray analysis showed that coho salmon-derived proteins were highly bound to serum IgE in Der p extract-sensitized mice. Serum IgE from Der p or Der f extract-sensitized mice was bound to coho salmon extract, whereas serum IgE from coho salmon extract-sensitized mice was bound to Der p or Der f extract. Analysis of the murine model showed that cutaneous anaphylaxis and oral allergic reaction were evident in Der p extract-sensitized mice stimulated by coho salmon extract. Serum IgE from Der p or Der f extract-sensitized mice was bound strongly to protein fractions separated by anion exchange chromatography of coho salmon proteins precipitated with 50% ammonium sulfate, which massively contained the approximately 38 kDa protein. We found that serum IgE from Der p extract-sensitized mice was bound to recombinant coho salmon tropomyosin. Der p extract-sensitized mice exhibited cutaneous anaphylaxis in response to coho salmon tropomyosin. Conclusion: Our results showed IgE cross-reactivity of tropomyosin between Dermatophagoides and coho salmon which illustrates salmon allergy following sensitization with the house dust mite Dermatophagoides. Our method for identifying IgE cross-reactive allergens will help understand the underlying mechanisms of food allergies.

Staphylococcus aureus δ-toxin present on skin promotes the development of food allergy in a murine model.

Background: Patients with food allergy often suffer from atopic dermatitis, in which Staphylococcus aureus colonization is frequently observed. Staphylococcus aureus δ-toxin activates mast cells and promotes T helper 2 type skin inflammation in the tape-stripped murine skin. However, the physiological effects of δ-toxin present on the steady-state skin remain unknown. We aimed to investigate whether δ-toxin present on the steady-state skin impacts the development of food allergy. Material and methods: The non-tape-stripped skins of wild-type, KitW-sh/W-sh, or ST2-deficient mice were treated with ovalbumin (OVA) with or without δ-toxin before intragastric administration of OVA. The frequency of diarrhea, numbers of jejunum or skin mast cells, and serum levels of OVA-specific IgE were measured. Conventional dendritic cell 2 (cDC2) in skin and lymph nodes (LN) were analyzed. The cytokine levels in the skin tissues or culture supernatants of δ-toxin-stimulated murine keratinocytes were measured. Anti-IL-1α antibody-pretreated mice were analyzed. Results: Stimulation with δ-toxin induced the release of IL-1α, but not IL-33, in murine keratinocytes. Epicutaneous treatment with OVA and δ-toxin induced the local production of IL-1α. This treatment induced the translocation of OVA-loaded cDC2 from skin to draining LN and OVA-specific IgE production, independently of mast cells and ST2. This resulted in OVA-administered food allergic responses. In these models, pretreatment with anti-IL-1α antibody inhibited the cDC2 activation and OVA-specific IgE production, thereby dampening food allergic responses. Conclusion: Even without tape stripping, δ-toxin present on skin enhances epicutaneous sensitization to food allergen in an IL-1α-dependent manner, thereby promoting the development of food allergy.

Association between Antibiotic Exposure and Type 2 Diabetes Mellitus in Middle-Aged and Older Adults.

BACKGROUND: Although previous studies have shown an association between clinically used antibiotics and type 2 diabetes, the relationship between antibiotic exposure from food and drinking water and type 2 diabetes in middle-aged and older adults is unclear. OBJECTIVE: This study was aimed at exploring the relationship between antibiotic exposures from different sources and type 2 diabetes in middle-aged and older people, through urinary antibiotic biomonitoring. METHODS: A total of 525 adults who were 45-75 years of age were recruited from Xinjiang in 2019. The total urinary concentrations of 18 antibiotics in five classes (tetracyclines, fluoroquinolones, macrolides, sulfonamides and chloramphenicol) commonly used in daily life were measured via isotope dilution ultraperformance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry. The antibiotics included four human antibiotics, four veterinary antibiotics and ten preferred veterinary antibiotics. The hazard quotient (HQ) of each antibiotic and the hazard index (HI) based on the mode of antibiotic use and effect endpoint classification were also calculated. Type 2 diabetes was defined on the basis of international levels. RESULTS: The overall detection rate of the 18 antibiotics in middle-aged and older adults was 51.0%. The concentration, daily exposure dose, HQ, and HI were relatively high in participants with type 2 diabetes. After model adjustment for covariates, participants with HI > 1 for microbial effects (OR = 3.442, 95%CI: 1.423-8.327), HI > 1 for preferred veterinary antibiotic use (OR = 3.348, 95%CI: 1.386-8.083), HQ > 1 for norfloxacin (OR = 10.511, 96%CI: 1.571-70.344) and HQ > 1 for ciprofloxacin (OR = 6.565, 95%CI: 1.676-25.715) had a higher risk of developing type 2 diabetes mellitus. CONCLUSIONS: Certain antibiotic exposures, mainly those from sources associated with food and drinking water, generate health risks and are associated with type 2 diabetes in middle-aged and older adults. Because of this study's cross-sectional design, additional prospective studies and experimental studies are needed to validate these findings.

Exposure of Tibetan pregnant women to antibiotics in China: A biomonitoring-based study.

Tibetan people are one Chinese ethnic minority living in Qinghai-Tibet Plateau with an average altitude of more than 4500 m. High altitude could cause a different antibiotic exposure, but relevant information is limited in Tibetan people. We investigated 476 Tibetan pregnant women in Lhasa, Tibet in 2021 and measured 30 antibiotics from five categories in urine, including 13 veterinary antibiotics (VAs), five human antibiotics (HAs), and 12 human/veterinary antibiotics (H/VAs). Food consumption was investigated by a brief food frequency questionnaire. Health risk was assessed by hazard quotient (HQ) and hazard index (HI) based on acceptable daily intakes (ADIs). All antibiotics were overall detected in 34.7% of urine samples with the 75th percentile concentration of 0.19 ng/mL (0.35 µg/g creatinine). HAs, VAs, and H/VAs were respectively detected in 5.3%, 13.0%, and 25.0% of urine samples, with the 95th percentiles of 0.01 ng/mL (0.01 µg/g creatinine), 0.50 ng/mL (0.99 µg/g creatinine), and 3.58 ng/mL (5.02 µg/g creatinine), respectively. Maternal age, smoking of family members, and housework time were associated with detection frequencies of HAs, VAs, or sum of all antibiotics. Pregnant women with a more frequent consumption of fresh milk, egg, yoghourt, poultry meat, and fish had a higher detection frequency of VAs or H/VAs. Only ciprofloxacin and tetracycline had a HQ of larger than one based on microbiological effect in 1.26% and 0.21% of pregnant women, respectively and a HI of larger than one was found in 1.47% of pregnant women. The findings suggested that there was an evident antibiotic exposure from various sources in Tibetan pregnant women with some basic characteristics of pregnant women as potential predictors and several animal-derived food items were important sources of exposure to antibiotic with a fraction of pregnant women in the health risk related to microbiological disruption of gut microbiota.

Maternal blood parameters and risk of neonatal pathological jaundice: a retrospective study.

This study aims to investigate the association between maternal blood parameters and the risk of neonatal pathological jaundice. A retrospective case-control study of 1309 newborns and their mothers from 2019 to 2020 in a single-center tertiary hospital. All mothers received a complete routine blood test prior to delivery, and outcome was neonatal pathological jaundice. We performed stepwise logistic regression modeling to identify maternal blood factors associated with neonatal pathological jaundice. 258 neonates (19.71%) were diagnosed with pathological jaundice. Logistic regression results showed that the odds ratio for pathological jaundice in neonates of mothers with high white blood cell (WBC) count was 1.512 (95% CI 1.145-1.998; P = 0.004). Besides, neonates whose mothers had a high mean corpuscular volume (MCV) during pregnancy doubled the odds of developing pathological jaundice (OR = 1.967; 95% CI 1.043-3.711; P = 0.037). Among neonates, those whose mothers had high levels of WBC count and MCV were at increased risk of pathological jaundice. Regular obstetric examinations and routine blood tests are essential to initiate adapted care.

Gestational exposure to perfluoroalkyl substances is associated with placental DNA methylation and birth size.

DNA methylation is one potential mechanism for the effects of gestational exposure to perfluoroalkyl substances (PFASs) on fetal growth. We investigated 180 pregnant women who participated in a cohort study conducted in Tangshan City, Northern China, and determined the concentrations of 11 PFASs and the methylation of two genes related to fetal growth [insulin-like growth factor 2 (IGF2) and nuclear receptor subfamily 3 group C member 1 (NR3C1)] and one surrogate marker for global methylation [long interspersed nuclear element-1 (LINE-1)] in placenta tissue. Multiple linear regression analysis was performed to examine the associations of log transformed PFASs with the DNA methylation and birth size. Weighted quantile sum regression was used to determine the mixture effect of PFASs. After adjusting for potential confounders, perfluorooctane sulfonate (PFOS) was negatively associated with the overall methylation of LINE-1. PFASs mixture was negatively associated with the methylation of all CpG loci of LINE-1 and overall methylation of NR3C1. Perfluorootanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and the PFASs mixture showed negative associations with head circumference. After stratified by newborns' sex, PFOA, PFNA and the PFASs mixture was negatively associated with overall methylation of LINE-1 only in the male subgroup and the methylation of all CpG loci of LINE-1 was negatively associated with ponderal index only in the female subgroup. The interaction of newborns' sex with PFOS and PFOA on overall methylation of IGF2 was statistically significant and so was the interaction of sex with PFOS on overall methylation of LINE-1. These findings suggested that intrauterine exposure to PFASs affected placental DNA methylation and reduced fetal growth, which might be modified by sex.

Urinary Antibiotics and Dietary Determinants in Adults in Xinjiang, West China.

The Xinjiang autonomous region, located in west China, has a unique ethnic structure and a well-developed livestock industry. People in this region have a high risk of exposure to antibiotics, but the exposure level to antibiotics in relation to dietary determinants is unknown. In this study, 18 antibiotics, including four human antibiotics (HAs), four veterinary antibiotics (VAs), and 10 preferred veterinary antibiotics (PVAs) were detected in the urine of approximately half of the 873 adults in Xinjiang, including Han Chinese (24.6%), Hui (25.1%), Uighur (24.6%), and Kazakh (25.7%). Logistic regression was used to analyze the association between antibiotic exposure levels and adult diet and water intake. The detection percentage of antibiotics in the urine of adults in Xinjiang ranged from 0.1% to 30.1%, with a total detection percentage of all antibiotics of 49.8%. HAs, VAs and PVAs were detected in 12.3%, 10.3%, and 40.5%, respectively. Fluoroquinolones were the antibiotics with the highest detection percentage (30.1%) and tetracyclines were the antibiotics with the highest detected concentration (17 ng/mL). Adults who regularly ate pork, consumed fruit daily, and did not prefer a plant-based diet were associated with thiamphenicol, norfloxacin, and fluoroquinolones, respectively. These results indicated that adults in the Xinjiang autonomous region were extensively exposed to multiple antibiotics, and some types of food were potential sources of exposure. Special attention should be paid to the health effects of antibiotic exposure in humans in the future.

Machine Learning and Swarm Optimization Algorithm in Temperature Compensation of Pressure Sensors.

The main temperature compensation method for MEMS piezoresistive pressure sensors is software compensation, which processes the sensor data using various algorithms to improve the output accuracy. However, there are few algorithms designed for sensors with specific ranges, most of which ignore the operating characteristics of the sensors themselves. In this paper, we propose three temperature compensation methods based on swarm optimization algorithms fused with machine learning for three different ranges of sensors and explore the partitioning ratio of the calibration dataset on Sensor A. The results show that different algorithms are suitable for pressure sensors of different ranges. An optimal compensation effect was achieved on Sensor A when the splitting ratio was 33.3%, where the zero-drift coefficient was 2.88 × 10-7/°C and the sensitivity temperature coefficient was 4.52 × 10-6/°C. The algorithms were compared with other algorithms in the literature to verify their superiority. The optimal segmentation ratio obtained from the experimental investigation is consistent with the sensor operating temperature interval and exhibits a strong innovation.

Neonicotinoids residues in the honey circulating in Chinese market and health risk on honey bees and human.

China is the largest beekeeping and honey consumption country globally. Neonicotinoids in honey can pose adverse effects on honey bees and human, but data on neonicotinoids residues in honey and its health risk remain limited in China. A total of 94 honey samples were selected from Chinese market based on production region and sale volume in 2020. Eight neonicotinoids and four metabolites were determined by liquid chromatography coupled to mass spectrometry. Health risk of neonicotinoids in honey on honey bees and human was assessed by hazard quotient (HQ) and hazard index (HI). Neonicotinoids and their metabolites were overall detected in 97.9% of honey samples. Acetamiprid, thiamethoxam, and imidacloprid were top three dominant neonicotinoids in honey with the detection frequencies of 92.6%, 90.4%, and 73.4%, respectively. For honey bees, 78.7% of honey samples had a HI larger than one based on the safety threshold value of sublethal effects. Top three neonicotinoids with the highest percent proportion of HQ larger than one for honey bees were acetamiprid (43.6%), imidacloprid (31.9%), and thiamethoxam (24.5%) and their maximum HQs were 420, 210, and 41, respectively. Based on oral median lethal doses for honey bees, both HQ and HI were lower than one in all honey samples. For human, both HQ and HI were lower than one based on acceptable daily intakes in all honey samples. Neonicotinoids concentrations and detection frequencies in honey samples and its health risk varied with production region, commercial value of nectariferous plants, number of nectariferous plants, and sale price. The results suggested extensive residues of neonicotinoids in honey in Chinese market with a variation by the characteristics of honey. The residues were likely to affect the health of honey bees, but showed no detectable effect on human health.

Development of mouse model for oral allergy syndrome to identify IgE cross-reactive pollen and food allergens: ragweed pollen cross-reacts with fennel and black pepper.

Oral allergy syndrome (OAS) is an IgE-mediated immediate food allergy that is localized to the oral mucosa. Pollen food allergy syndrome (PFAS), a pollinosis-associated OAS, is caused by cross-reactivity between food and pollen allergens. However, we need to more precisely understand the underlying pathogenesis of OAS/PFAS. In the present study, we developed a method to comprehensively identify cross-reactive allergens by using murine model of OAS and protein microarray technology. We focused on lip angioedema, which is one of the most common symptoms of OAS, and confirmed that mast cells reside in the tissues inside the lower lip of the mice. Interestingly, when the food allergen ovalbumin (OVA) was injected inside the lower lip of mice with high levels of OVA-specific IgE followed by an intravenous injection of the Evans blue dye, we found immediate dye extravasation in the skin of the neck in a mast cell-dependent manner. In addition, the degree of mast cell degranulation in the oral cavity, reflecting the severity of oral allergic responses, can be estimated by measuring the amount of extravasated dye in the skin. Therefore, we used this model of OAS to examine IgE cross-reactive allergens in vivo. Protein microarray analysis showed that serum IgE from mice intraperitoneally sensitized with ragweed pollen, one of the major pollens causing pollinosis, bound highly to protein extracts from several edible plants including black peppercorn and fennel. We confirmed that the levels of black pepper-specific IgE and fennel-specific IgE were significantly higher in the serum from ragweed pollen-sensitized mice than in the serum from non-sensitized control mice. Importantly, analysis of murine model of OAS showed that the injection of black pepper or fennel extract induced apparent oral allergic responses in ragweed pollen-sensitized mice. These results indicate IgE cross-reactivity of ragweed pollen with black pepper and fennel. In conclusion, we developed mouse model of OAS to identify IgE cross-reactive pollen and food allergens, which will help understand the pathogenesis of OAS/PFAS.

Antibiotic Use and Bacterial Infection in COVID-19 Patients in the Second Phase of the SARS-CoV-2 Pandemic: A Scoping Review.

This scoping review aimed to explore the prevalence and patterns of global antibiotic use and bacterial infection in COVID-19 patients from studies published between June 2020 and March 2021. This review was reported in line with the Preferred Reporting of Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews, and the protocol is registered with the Open Science Framework. Compared with our previously-published review of the period (December 2019-June 2020), the antibiotic prescribing rate for COVID-19 patients (June 2020-March 2021) was found to have declined overall (82.3% vs. 39.7%), for mild and moderate patients (75.1% vs. 15.5%), and for severe and critical patients (75.3% vs. 48.3%). The seven most frequently prescribed antibiotics in COVID-19 patients were all on the "Watch" list of the WHO AWaRe antibiotics classification. The overall reported bacterial infection rate in COVID-19 patients was 10.5%, and the most frequently reported resistant pathogen in COVID-19 patients was Staphylococcus aureus, followed by Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae. There is an urgent need to establish comprehensive and consistent guidelines to assist clinicians in selecting appropriate antibiotics for COVID-19 patients when needed. The resistance data on the most frequently used antibiotics for COVID-19 patients for certain resistant pathogens should be closely monitored.

Impacts of Antibiotic Residues in the Environment on Bacterial Resistance and Human Health in Eastern China: An Interdisciplinary Mixed-Methods Study Protocol.

Antibiotic resistance is a global health challenge that threatens human and animal lives, especially among low-income and vulnerable populations in less-developed countries. Its multi-factorial nature requires integrated studies on antibiotics and resistant bacteria in humans, animals, and the environment. To achieve a comprehensive understanding of the situation and management of antibiotic use and environmental transmission, this paper describes a study protocol to document human exposure to antibiotics from major direct and indirect sources, and its potential health outcomes. Our mixed-methods approach addresses both microbiological and pathogen genomics, and epidemiological, geospatial, anthropological, and sociological aspects. Implemented in two rural residential areas in two provinces in Eastern China, linked sub-studies assess antibiotic exposure in population cohorts through household surveys, medicine diaries, and biological sampling; identify the types and frequencies of antibiotic resistance genes in humans and food-stock animals; quantify the presence of antibiotic residues and antibiotic resistance genes in the aquatic environment, including wastewater; investigate the drivers and behaviours associated with human and livestock antibiotic use; and analyse the national and local policy context, to propose strategies and systematic measurements for optimising and monitoring antibiotic use. As a multidisciplinary collaboration between institutions in the UK and China, this study will provide an in-depth understanding of the influencing factors and allow comprehensive awareness of the complexity of AMR and antibiotic use in rural Eastern China.

Exposure to perfluoroalkyl substances was associated with estrogen homeostasis in pregnant women.

Previous studies have suggested that perfluoroalkyl substances (PFASs) can act as endocrine disruptors, but few studies have investigated the effects of serum PFASs on estrogen homeostasis during pregnancy. The present study included 557 pregnant women in Tangshan City, North China, and determined 11 serum PFASs in the early term of pregnancy and three typical estrogens (estrone (E1), estradiol (E2) and estriol (E3)) in the early (n = 557), middle (n = 339), and late (n = 286) terms of pregnancy. Sociodemographic factors and diet information were obtained by structured questionnaires. After adjusting for potential confounders, multiple linear regression model demonstrated negative associations of natural logarithmic transformed serum perfluoroundecanoic acid (Ln PFUdA) with Ln E1and Ln E3 in the early term of pregnancy with ß coefficients of -0.060 (95% confidence interval (CI): -0.101 to -0.019) and -0.041 (95% CI: -0.070 to -0.011), respectively. Ln perfluorodecanoic acid (PFDA) was negatively associated with averaged E1 in the early and middle (EM) terms of pregnancy with a ß coefficient of -0.205 (95% CI: -0.357 to -0.053). Ln perfluorononanoic acid (PFNA) tended to be negatively associated with E2 in the late term of pregnancy with a ß coefficient of -0.134 (95% CI: -0.253 to -0.016) although p-value was slightly greater than 0.05 after false discovery rate (FDR) correction. Mixed effect model found that serum PFDA was negatively associated with E1 (ß = -0.123, 95% CI: -0.235 to -0.012) during the entire pregnancy. These findings suggested that exposure to PFASs disturbed estrogen homeostasis in pregnant women and the effects varied with the terms of pregnancy.

Urinary antibiotic level of school children in Shanghai, East China, 2017-2020.

In recent years, an extensive exposure to antibiotics from various sources has been demonstrated in China by the biomonitoring method, but the temporal trend remains little known. The study aim was to explore the temporal trend of exposure to antibiotics and associated health risk in children. A dynamic child cohort was established in Shanghai, East China between 2017 and 2020. A total of 684 school children aged 7-11 years were included, and 280 in 2017, 279 in 2018, 288 in 2019, and 287 in 2020 participated in annual surveys. Twenty-three typical antibiotics and three metabolites from five categories (four tetracyclines, five qinolones, six macrolides, eight sulfonamides, and three phenicols), bisphenol A (BPA), and monobutyl phthalate (MBP) were determined in urine. Logistic regression analysis with generalized estimating equations was conducted to investigate the associations between various variables and the detection frequency of antibiotics in urine. Seventeen antibiotics and three metabolites were found in 51.9% of all urine samples. Compared to 2017, the detection frequency in urine reduced 31.8% in 2020 for all antibiotics (58.2% vs 39.7%) and reduced 36.8%-55.8% for tetracyclines (11.4% vs 7.0%), qinolones (34.3% vs 21.3%), macrolides (8.6% vs 3.8%), sulfonamides (16.4% vs 8.7%), and phenicols (19.3% vs 12.2%). After accounting for personal characteristics, food consumption, and urinary BPA and MBP, a decreasing temporal trend of detection frequencies was observed from 2017 to 2020 for most antibiotics. Urinary concentration, estimated daily intake, and acceptable daily intake-based health risk of antibiotics showed a temporal trend similar to detection frequency. There was an extensive exposure to antibiotics in children. However, a decreasing temporal trend occurred for the exposure during the period from 2017 to 2020. The trend was likely to be caused by decreased antibiotic use and/or decreased residues in food and/or drinking water.

Association of triclosan and triclocarban in urine with obesity risk in Chinese school children.

BACKGROUND: Laboratory studies have suggested that triclosan and triclocarban can influence energy metabolism by multiple mechanisms and are potential obesogens, but the effect on obesity risk has not been well investigated in human. OBJECTIVE: To examine the associations of triclosan and triclocarban in urine with childhood obesity. METHODS: We investigated 458 school children aged 7-11 years who entered a dynamic cohort of children established in Shanghai in 2019 and 2020. Triclosan and triclocarban were determined in first morning urine by liquid chromatography coupled to mass spectrometry. Body mass index (BMI) and waist circumference (WC) were used to identify general overweight/obesity and central obesity, respectively. Logistic regression and linear models of generalized estimating equations (GEE) were used to investigate the association between urinary triclosan and triclocarban with obesity prevalence. RESULTS: After adjusting for potential confounders, children with detectable triclocarban in urine had a higher proportion of general overweight/obesity (odds ratio (OR): 1.84; 95% confidential interval (95% CI): 1.19, 2.85) or central obesity (OR: 1.71; 95% CI: 1.03, 2.84). Compared to the low tertile, children in the median tertile of triclosan showed a higher proportion of central obesity (OR: 1.78; 95 %CI: 0.98, 3.24) and children in the high tertile of triclocarban had a higher proportion of general overweight/obesity (OR: 2.25; 95 %CI: 1.31, 3.88) and central obesity (OR: 2.08; 95 %CI: 1.12, 3.87). When the tertiles of triclocarban in urine were treated as a continuous variable, a positive exposure-response relationship was found with general overweight/obesity (OR: 1.50; 95 %CI: 1.15, 1.96) and central obesity (OR: 1.44; 95 %CI: 1.06, 1.95). Multiple linear regression showed a positive exposure-response relationship between triclocarban and BMI (ß: 0.45; 95 %CI: 0.11, 0.80) values. CONCLUSION: Exposure to triclosan and triclocarban was associated with increased risk of childhood obesity. Given the cross-sectional design, more studies are needed to interrogate these findings.

Antimicrobial Use in COVID-19 Patients in the First Phase of the SARS-CoV-2 Pandemic: A Scoping Review.

This scoping review provides new evidence on the prevalence and patterns of global antimicrobial use in the treatment of COVID-19 patients; identifies the most commonly used antibiotics and clinical scenarios associated with antibiotic prescribing in the first phase of the pandemic; and explores the impact of documented antibiotic prescribing on treatment outcomes in COVID-19 patients. The review complies with PRISMA guidelines for Scoping Reviews and the protocol is registered with the Open Science Framework. In the first six months of the pandemic, there was a similar mean antibiotic prescribing rate between patients with severe or critical illness (75.4%) and patients with mild or moderate illness (75.1%). The proportion of patients prescribed antibiotics without clinical justification was 51.5% vs. 41.9% for patients with mild or moderate illness and those with severe or critical illness. Comparison of patients who were provided antibiotics with a clinical justification with those who were given antibiotics without clinical justification showed lower mortality rates (9.5% vs. 13.1%), higher discharge rates (80.9% vs. 69.3%), and shorter length of hospital stay (9.3 days vs. 12.2 days). In the first 6 months of the pandemic, antibiotics were prescribed for COVID-19 patients regardless of severity of illness. A large proportion of antibiotic prescribing for mild and moderate COVID-19 patients did not have clinical evidence of a bacterial co-infection. Antibiotics may not be beneficial to COVID-19 patients without clinical evidence of a bacterial co-infection.