Probable Evidence of Fecal Aerosol Transmission of SARS-CoV-2 in a High-Rise Building.

BACKGROUND: The role of fecal aerosols in the transmission of severe acute respiratory syndrome coronavirus 2 has been suspected. OBJECTIVE: To investigate the temporal and spatial distributions of 3 infected families in a high-rise apartment building and examine the associated environmental variables to verify the role of fecal aerosols. DESIGN: Epidemiologic survey and quantitative reverse transcriptase polymerase chain reaction analyses on throat swabs from the participants; 237 surface and air samples from 11 of the 83 flats in the building, public areas, and building drainage systems; and tracer gas released into bathrooms as a surrogate for virus-laden aerosols in the drainage system. SETTING: A high-rise apartment building in Guangzhou, China. PARTICIPANTS: 9 infected patients, 193 other residents of the building, and 24 members of the building's management staff. MEASUREMENTS: Locations of infected flats and positive environmental samples, and spread of virus-laden aerosols. RESULTS: 9 infected patients in 3 families were identified. The first family had a history of travel to the coronavirus disease 2019 (COVID-19) epicenter Wuhan, whereas the other 2 families had no travel history and a later onset of symptoms. No evidence was found for transmission via the elevator or elsewhere. The families lived in 3 vertically aligned flats connected by drainage pipes in the master bathrooms. Both the observed infections and the locations of positive environmental samples are consistent with the vertical spread of virus-laden aerosols via these stacks and vents. LIMITATION: Inability to determine whether the water seals were dried out in the flats of the infected families. CONCLUSION: On the basis of circumstantial evidence, fecal aerosol transmission may have caused the community outbreak of COVID-19 in this high-rise building. PRIMARY FUNDING SOURCE: Key-Area Research and Development Program of Guangdong Province and the Research Grants Council of Hong Kong.

Human Sex Hormone Disrupting Effects of New Flame Retardants and Their Interactions with Polychlorinated Biphenyls, Polybrominated Diphenyl Ethers, a Case Study in South China.

Even though sex hormone disrupting effects of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are widely understood, similar effects associated with new flame retardants (NFRs) have not been so well studied. This study aimed to explore the sex hormone disruption of NFRs and their interactions with PCBs and PBDEs through the conduct of an ecological study in an e-waste dismantling and control region in South China. Questionnaires and blood samples were collected from local adult residents. Results of generalized additive model and linear regression analyses indicate that several species of NFRs showed similar disrupting effects with PBDE congeners on female follicle-stimulating hormone (FSH) and male testosterone. Judged by the curved shape and statistical significance, ΣNFR (sum of 8 species of NFRs) showed stronger disrupting effects on male testosterone and female FSH compared to ΣPBDE (sum of 13 congeners of PBDEs). The interactions induced by NFRs complicated the original sex hormone disruption led by PCBs and PBDEs. The disrupting effects and interactions induced by NFRs decreased female FSH levels in the exposed group. Comprehensive evaluation is needed to provide the evidence base for judging the health risks arising from the increased usage of NFRs.

Role of lens in early refractive development: evidence from a large cohort of Chinese children.

AIMS: To document longitudinal changes in spherical equivalent refraction (SER) and related biometric factors during early refractive development. METHODS: This was a prospective cohort study of Chinese children, starting in 2018 with annual follow-ups. At each visit, children received cycloplegic autorefraction and ocular biometry measurements. Lens power (LP) was calculated using Bennett's formula. Children were divided into eight groups based on baseline age: the 3-year-old (n=426, 49.77% girls), 4-year-old (n=834, 47.36% girls), 6-year-old (n=292, 46.58% girls), 7-year-old (n=964, 43.46% girls), 9-year-old (n=981, 46.18% girls), 10-year-old (n=1181, 46.32% girls), 12-year-old (n=504, 49.01%) and 13-year-old (n=644, 42.70%) age groups. RESULTS: This study included right-eye data from 5826 children. The 3-year-old and 4-year-old age groups demonstrated an inflection point in longitudinal SER changes at a mild hyperopic baseline SER (+1 to +2 D), with children with more myopic SER showing hyperopic refractive shifts while those with more hyperopic SER showing myopic shifts. The hyperopic shift in SER was mainly attributed to rapid LP loss and was rarely seen in the older age groups. Axial elongation accelerated in the premyopia stage, accompanied by a partially counter-balancing acceleration of LP loss. For children aged 3-7 years, those with annual SER changes <0.25 D were all mildly hyperopic at baseline (mean: 1.23 D, 95% CI 1.20 to 1.27 D). CONCLUSION: Our findings suggest that during early refractive development, refractions cluster around or above +1.00 D. There is a pushback process in which increases in the rate of LP occur in parallel with increases in axial elongation.

Effect of Extracurricular After-School Physical Activities on Academic Performance of Schoolchildren: A Cluster Randomized Clinical Trial.

Importance: The beneficial effects of increasing outdoor physical activity time on children's myopia onset and physical well-being are widely acknowledged. However, in countries with competitive educational systems, such as China, parents and school administrators may be relatively reluctant to increase the extracurricular physical activity time for children due to concerns that this action will compromise children's academic performance. Objective: To investigate whether additional extracurricular physical activity time after school compromises the academic performance of schoolchildren. Design, Setting, and Participants: This cluster randomized clinical trial was conducted from October 2020 to June 2021 in Yudu, Jiangxi, China. Eligible children in grades 3 and 4 from 24 elementary schools were randomized to the intervention or control group. Primary analysis was conducted in the full sample using the intention-to-treat principle. Interventions: The intervention group received 2 hours of after-school physical activity time outdoors on school days. The control group was free to arrange their after-school activity. Main Outcomes and Measures: The primary outcome was the between-group mean difference in mathematics test scores at the end of 1 academic year, with a noninferiority margin of -3.3 points. Standardized mathematics tests, physical fitness assessments (in reference to the 2018 National Physical Fitness Survey Monitoring Programme in China), and cycloplegic autorefraction were performed at baseline and the end of 1 academic year. Myopia was defined as a cycloplegic spherical equivalent refraction of -0.5 diopters or less in either eye. Results: A total of 2032 children (mean [SD] age, 9.22 [0.62] years; 1040 girls [51.2%]) from 24 schools were randomized to the intervention group (12 schools; 1012 children) or control group (12 schools; 1020 children). The mean (SD) mathematics score at the end of 1 academic year was 78.01 (17.56) points in the intervention group and 77.70 (17.29) points in the control group. The adjusted between-group mean difference was 0.65 points (95% CI, -2.85 to 4.15). The adjusted between-group mean difference in physical fitness score was 4.95 points (95% CI, 3.56-6.34; P < .001) and -1.90% (95% CI, -18.72% to 14.91%; P > .99) in myopia incidence. Conclusions and Relevance: Results of this trial indicate that, compared with the control practice of free play after school, adding 2 hours of extracurricular physical activity outdoors after school was noninferior in academic performance and had superior efficacy in improving physical fitness. Trial Registration: ClinicalTrials.gov Identifier: NCT04587765.

Longitudinal Changes in Lens Thickness and Lens Power Among Persistent Non-Myopic and Myopic Children.

Purpose: To assess the longitudinal changes in crystalline lens in persistent non-myopic and myopic children. Methods: Four cohorts of children were recruited from Guangzhou, China, from first year of kindergarten (G0, n = 1129), first year of primary school (G1, n = 1324), fourth year of primary school (G4, n = 1854), and first year of junior high school (G7, n = 867) in 2018 and followed up annually for 2 years. All children received cycloplegic autorefraction and ocular biometry measurement. Children were classified into categories of persistent non-myopia (PNM; spherical equivalent refraction [SER] ≥-0.5 diopter [D] at baseline and during follow-up), persistent myopia (PM; SER <-0.5 D at baseline and during follow-up), or newly developed myopia (NDM: SER ≥-0.5 D at baseline and <-0.5 D during follow-up). Results: The mean (SD) age was 3.69 (0.34) years for children in G0, 6.79 (0.35) years in G1, 9.52 (0.42) years in G4, and 12.56 (0.38) years in G7. A LOWESS plot showed a three-stage pattern of change in lens thickness (LT) in PNM children including a rapid decrease from 3 to 7 years of age and a slower decrease from 7 to 11 years, followed by an increase thereafter. Similar trends were observed in the PM and NDM groups, although there was less change in LT. In contrast, lens power (LP) decreased consistently in all cohorts during the follow-up. No significant changes in LT or LP were observed around myopia onset. Conclusions: The lens showed a three-stage pattern of change in LT, whereas there was continuous loss of LP in children ages 3 to 15 years.

Axial Growth Driven by Physical Development and Myopia among Children: A Two Year Cohort Study.

Background: The physical process of axial length growth among children and its role in the occurrence of myopia remain insufficiently explored. In this study, we investigate the patterns of ocular axial growth among persistent myopia (PM) and persistent non-myopia (PNM) children aged 3 to 15 years. Methods: A group of 6353 children aged 3 to 15 years, selected from rural schools in China, were followed up annually for 2 years. Biometric measurements including axial length (AL) and spherical equivalent refraction (SER) were obtained. Body height was recorded. Children were divided into two groups: PM group defined as SER of −0.50 D or less; PNM group defined as −0.50 D < SER < +3.0 D during follow-up. Results: Annual AL growth was fairly consistent for PNM eyes of children aged 3 to 11 years and then reduced significantly (independent t test, p < 0.001) for children aged 12 years and older. This pattern of AL changes was similar for PM children, although the AL growth was greater among them. Among children aged 6 and older, body height change was concomitant to AL growth (p < 0.01) and SER myopic shift (p < 0.001) until reaching 12 years old (p = 0.308 and p = 0.679, respectively). Conclusions: Stature growth and AL growth are both remarkable and consistent and concomitant but start to attenuate when the children reach 10 to 12 years old among emmetropic children. This observation suggests that AL growth is driven by physical development until 12 years old, whereas its excessive growth is dominated by myopia development.

[Genetic susceptibility of DNA damage induced by vinyl chloride monomer exposure].

OBJECTIVE: To explore the association between DNA damage induced by vinyl chloride monomer (VCM) and polymorphisms of DNA repair genes and xenobiotic metabolism genes of VCM. METHODS: Comet assay was employed to detect DNA damage. Based on the status of DNA damage, the VCM exposure workers were divided into two groups: DNA damage group (75) and control group (75). Case-control design was used to investigate the association between the genetic polymorphisms and DNA damage induced by VCM. Genotypes of XRCC1 (Arg194Trp, Arg280His and Arg399Gln), XPD (Ile199Met, Asp312Asn and Lys751Gln) and CYP2E1 were identified by the PCR-RFLP. PCR assay was used to detect positive and null genotype of GSTT1 and GSTM1. RESULTS: Univariate analysis showed that the CYP2E1 c1c2/c2c2 and XPD751 Lys/Gln and Gln/Gln genotypes were significantly associated with the increased levels of DNA damage, XRCCI 339 Arg/Gln and Gln/Gln genotypes were significantly associated with the decreased levels of DNA damage (P < 0.01, P < 0.05, respectively). Logistic regression analysis showed that there was significant association between the genotypes of XRCC1 194, XRCC1 399, XPD 751, CYP2E1 and DNA damages. A prominent risk decreasing of DNA damage was observed for those individuals possessing XRCC1 399Arg/Gln + Gln/Gln genotypes (OR: 0.35, 95%CI: 0.12 approximately 1.01, respectively); The results also showed that there were significant associations between CYP2E1 c1c2/c2c2 and DNA damage both in high and low VCM-exposed groups (OR: 2.57, 95%CI: 1.01 approximately 6.59 and OR: 2.57, 95%CI: 0.99 approximately 6.87). CONCLUSION: Cumulative exposure dose and genotypes of XRCC1 194, XRCC1 399, XPD 751 and CYP2E1 may modulate the DNA damage induced by VCM exposure.

Genetic polymorphisms of IL-1A, IL-1B, IL-1RN, NFKB1, FAS, and FASL, and risk of silicosis in a Chinese occupational population.

OBJECTIVE: To test whether polymorphisms in IL-1, NF-KB, FAS, and FASL genes are associated with risk of silicosis. METHODS: A case-control study was conducted with 183 silicosis patients and 111 silica-exposed miners who were frequency-matched by age, dust exposure duration, work location, and type of work. Genotype analysis was performed on genomic DNA, using a PCR-RFLP assay. RESULTS: Individuals carrying the NFKB1 ins/del genotype had a decreased risk of silicosis (adjusted OR = 0.57, 95% CI = 0.32-0.998, P = 0.049) compared with subjects carrying the ins/ins genotype and individuals with the FAS-1377AA homozygote had a decreased risk of silicosis compared with those with the -1377GG genotype (adjusted OR = 0.42, 95% CI = 0.19-0.93, P = 0.03). The analysis of haplotypes of polymorphisms in FAS showed that there was a 2.71-fold (OR = 2.71, 95% CI = 1.22-6.03, P = 0.011) increased risk of silicosis for subjects with alleles of FAS-1377G and FAS-670G, compared with those carrying alleles of FAS-1377G and FAS-670A. CONCLUSION: Although the polymorphisms at NFKB1, FAS-1377, and extended haplotype FAS-1377G/-670G may play a role in the development of silicosis in the Chinese population, our findings should be verified by larger studies with >1 case/control ratio.

CYP2E1 mRNA expression, genetic polymorphisms in peripheral blood lymphocytes and liver abnormalities in Chinese VCM-exposed workers.

OBJECTIVE: To study the relationship between expression of cytochrome P4502E1 (CYP2E1) in human lymphocytes, variant CYP2E1 genotype, exposure to vinyl chloride monomer (VCM), and liver abnormalities in VCM-exposed workers. METHODS: A case-control study was performed on 90 male occupationally exposed workers and 42 matched male nonexposed controls. Data were collected based on health surveillance, workplace investigation and questionnaire Survey. Total RNA and DNA were isolated from peripheral blood lymphocytes, and CYP2E1 mRNA expression was determined using RT-PCR, and the presence of CYP2E1 polymorphisms was identified based on PCR-RFLP. RESULTS: The mRNA expression of CYP2E1 in exposed workers (0.89+/-0.46) was significantly higher than in nonexposed controls (0.61+/-0.35) (P < 0.01). Logistic regression analysis demonstrated a statistically significant association between CYP2E1 mRNA expression levels and liver abnormalities in the VCM-exposed workers (OR = 3.66, P < 0.05). The genotype frequency for CYP2E1 variants among VCM-exposed workers was not significantly different between workers with liver abnormalities and those without. CONCLUSIONS: Liver abnormalities in subjects exposed to VCM are positively associated with expression of peripheral blood lymphocyte mRNA, which is significantly increased in exposed workers compared to nonexposed controls. Therefore, CYP2E1 mRNA levels may be useful for health surveillance and protection of VCM-exposed workers.

[Polymorphisms of FAS and FASL genes and susceptibility of silicosis].

OBJECTIVE: To explore the relationship between polymorphisms of FAS and FASL genes and genetic susceptibility of silicosis. METHODS: A case-control study was conducted. The case group was 183 male patients with silicosis and the control group was 111 male silica-exposed but without silicosis miners. Data on total dust concentrations was collected to estimate cumulative total dust exposure (CTE) of each subject and each person's characteristics and work history were obtained from questionnaire. Polymerase chain reaction re-strained fragment length polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide polymorphisms (SNPs) of FAS-1377, FAS-670 and FASL-844. Associations between polymorphisms and risk of silicosis and stages, interactions between polymorphisms, between polymorphisms and CTE and smoking and haplotypes were analyzed. RESULTS: There were no differences in the FAS-1377, FAS-670 and FASL-844 genotypes between the case group and the control group (P > 0.05). No association was observed between FAS-1377, FAS-670 and FASL-844 polymorphisms and silicosis and stages (P > 0.05). The frequencies of FAS-1377G/-670G haplotype in the cases (9.6%) were higher than those in the controls (3.6%) (P < 0.05). No interactions between the polymorphisms of different genes, the gene polymorphism and the total accumulative total dust, the gene polymorphism and smoking were observed (P > 0.05). CONCLUSION: FAS-1377, FAS-670 and FASL-844 polymorphisms are not susceptible factors of silicosis. The FAS-1377G/-670G haplotype might be a susceptibility marker of silicosis.

Genetic polymorphisms in alveolar macrophage response-related genes, and risk of silicosis and pulmonary tuberculosis in Chinese iron miners.

Alveolar macrophages (AMs) play a prominent role in influencing the development of lung inflammation and injury. The aim of this study is to investigate the roles of AMs response-related genes TNF-alpha, iNOS, and NRAMP1 (SLC11A1) in susceptibility to silicosis and pulmonary tuberculosis (PTB), and to analyze the interaction of dust exposure and genetic susceptibility to silicosis, interactions of TNF-alpha-308 and Natural Resistance-associated Macrophage Protein 1 (NRAMP1) INT4, D543N polymorphisms to PTB. Several epidemiological designs were used: retrospective investigations on dust exposure, case-control studies of 184 silicosis cases and 111 miners occupationally exposed to silica dust, and 1:2 matched case-control studies of 61 PTB cases and 122 PTB-free miners. The miners and controls were recruited from an iron mining operation in Anhui province, China. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was applied to detect single nucleotide polymorphisms. Despite the recruitment of high dust exposure among the controls, silicosis patients still had significantly higher dust exposure than controls (242.6 +/- 98.8 vs. 217.6 +/- 100.7 mg a/m(3)). The mutation of iNOS Ser608Leu is associated with protection against silicosis and against severity of silicosis in the miners. There is a 0.47-fold (95% CI: 0.28-0.79) decrease in risk of silicosis for individuals with C/T, T/T genotype compared with the wild-type homozygous (C/C) individuals after adjustment for occupational exposure, smoking, and drinking. The protection effect of the iNOS polymorphism was particularly detected in the > or = 150 mg a/m(3) exposure group (OR: 0.44, 95% CI: 0.22-0.91). However, no interaction of dust exposure with the iNOS polymorphism was observed. Furthermore, the variant NRAMP1 INT4 genotype is significantly associated with PTB in miners. No association of other polymorphisms (NRAMP1 D543N, TNF-alpha-308) and susceptibility to silicosis or PTB in Chinese miners was found. Our data showed a 3.26-fold (95% CI: 1.47-7.23) increased risk of PTB for miners carrying both the NRAMP1 D543N G/G and NRAMP1 INT4 G/C+C/C genotypes. Additionally, in miners with TNF-alpha-308 G/G genotype, the risk of PTB increased 2.38-fold if they carry the NRAMP1 INT4 G/C+C/C genotype (95% CI: 1.14-4.98). In conclusion, the C>T mutation of iNOS Ser608Leu may be an important protective factor to miners. On the other hand, the variant NRAMP1 INT4 may play a role in the development of PTB in Chinese miners. Therefore, the novel information can be used as guideline for further mechanistic investigations and for strengthening specific protection protocols for workers.

[Relationship between single nucleotide polymorphisms of NRAMP1 gene and susceptibility to pulmonary tuberculosis in workers exposed to silica dusts].

OBJECTIVE: To explore the relationship between polymorphisms of natural resistance-associated macrophage protein 1 (NRAMP1) gene and genetic susceptibility of pulmonary tuberculosis (PTB) in workers exposed to silica dusts. METHODS: A 1:2 case control study of 61 male workers with PTB (50 silicosis patients and 11 unsilicosis workers) as the case group and 122 male PTB-free workers (100 silicosis patients and 22 unsilicosis workers) as the control group was conducted with the frequency matched for age of +/- 5 years, the job, the silica exposure, and the condition of cigarette smoking and alcohol drinking. The polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) was used to detect the single nucleotide polymorphisms (SNPs) of NRAMP1 INT4 and D543N. RESULTS: There was a 2.73 times (95% CI: 1.32 approximately 5.64) increased risk of silicosis for individuals with C allele of NRAMP1 INT4 compared with individuals carrying homozygote (G/G), while SNPs of NRAMP1 D543N was not associated with PTB (P > 0.05). CONCLUSION: The G > C mutation of intron 4 of NRAMP1 gene might be a susceptible factor of silica for the workers exposed to PTB.

Lack of association between cytokine gene polymorphisms and silicosis and pulmonary tuberculosis in Chinese iron miners.

Silicosis is a fibrotic lung disease produced by the inhalation and deposition of silica dust. The association between silicosis and pulmonary tuberculosis (PTB) has been well established. Cytokines participate in the development and progression of silicosis and PTB. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) gene at position -308; in the transforming growth factor-beta 1 (TGF-beta1) gene at positions -509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position -1,082, -819 and -592; and in the intron 1 of the interferon-gamma (IFN-gamma) gene at position +874 are associated with silicosis and PTB. We conducted a case-control study with 183 silicosis patients and 111 silica-exposed miners, and a 1:2 matched case-control study of 61 PTB cases and 122 PTB-free miners. Genotype analysis was performed on genomic DNA, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. There was complete linkage disequilibrium (LD) between the -819C and -592C alleles of the IL-10 gene. The genotype frequencies were similar between cases and control subjects for all investigated cytokine polymorphisms (p>0.05). We did not find an association between the different genotypes and severity of silicosis. We assume that these genetic variants do not play a dominant role in silicosis and PTB in our Chinese population.