Aberrant Splicing of COL4A5 Intronic Variant Contribute to the Pathogenesis of X-Linked Alport Syndrome: A Case Series.

Introduction: X-linked Alport syndrome (XLAS) is caused by pathogenic variants in COL4A5 which lead to abnormalities of the glomerular basement membrane (GBM) structural and is characterized by progressive kidney disease, hearing loss, and ocular abnormalities. The aim of this study was to identify gene mutations in a Chinese family with XLAS by whole-exome sequencing (WES) and verified the pathogenicity of the mutation in vitro experiments. Case Presentation: A five-generation pedigree with a total of 49 family members originating from Hainan province of China was investigated in this study. The proband was a 23-year-old male who developed microscopic hematuria, proteinuria and end-stage kidney disease (ESKD) at age 17. WES identified a novel splicing mutation c.321+5G>A of COL4A5, which cause exon skip. Further co-segregation analysis confirmed that this mutation exists in relatives who had renal abnormalities using Sanger sequencing. According to American College of Medical Genetics and Genomics guidelines (ACMG), the mutation was determined to be of uncertain significance (VUS). In vitro splicing experiments have shown that the COL4A5 variant induces aberrant mRNA splicing and transcript deletion. Conclusion: We identified a novel intronic COL4A5 pathogenic mutation (c.321+5G>A) in a Chinese XLAS family and described the phenotypes of affected relatives. This study expands the mutation spectrum of COL4A5 gene in XLAS and demonstrates the importance of gene screening for AS.

The association of low serum uric acid with mortality in older people is modified by kidney function: National Health and Nutrition Examination Survey (NHANES) 1999-2018.

BACKGROUND: In older individuals, the role of low serum uric acid (SUA) as risk factor for mortality is debated. We therefore studied whether SUA levels, particularly low SUA concentrations, are associated with all-cause and cardiovascular (CV) mortality in older population, and to clarify potential effect modification of kidney function. METHODS: We identified 14,005 older people in National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018. SUA was measured only at baseline. The relationship between SUA and mortality was assessed using Cox proportional hazards models and restricted cubic spline Cox regression stratified by the estimated glomerular filtration rate (eGFR). RESULTS: During mean 8.3 years of follow-up, 4852 all-cause death and 1602 CV death were recorded. A significant U-shaped association was observed between SUA with all-cause mortality, with the lowest risk concentration of 5.5 mg/dL. Comparing to the reference group (5 to 7 mg/dL), the HR of 2 to < 5 mg/dL group was 1.11 (1.03-1.21) and 1.14 (1.00-1.30). This relationship was more pronounced in participants with an eGFR ≥ 60 ml/min/1.73m2 (HR, 1.16; 95%CI, 1.06-1.28). This situation similarly occurred in Urine protein negative group (HR, 1.14; 95%CI, 1.04-1.25). CONCLUSIONS: Low SUA concentrations are associated with an increased risk in all-cause and CV mortality among older participants. Extremely low SUA concentrations are especially undesirable, especially in the older adults with normal kidney function.

What Works for Controlling Meningitis Outbreaks: A Case Study from China.

The meningococcal meningitis (MM) vaccine reduces the incidence of MM significantly; however, outbreaks still occur in communities with high vaccine coverage. We aimed to analyze the driving factors of infection from a community outbreak. A total of 266 children aged 9 to 15 years old from the three junior high schools of Tongzi county were identified. We documented infection cases using laboratory tests and analyzed attack rates, infection rates and risk factors for transmission. The index case in School A was identified, and the attack rate in School A was 0.03%. Children showed a significantly low infection rate of MenC in School A (13.2% vs. 19.5% in total children, p = 0.002), while exhibiting significantly high infection rates of MenA in School B (44.1% vs. 24.8% in total children, p < 0.001) and MenB in School C (11.1% vs. 4.1% in total children, p = 0.015). The infection rate of MenA for females (30.0%) was higher (p = 0.055) than for males (19.9%). In School A, 63.19% of children were vaccinated against MenC, while in School B the rate was 42.65% and in School C, it was 59.26%. Three male MenC infection cases were detected as breakthrough infection cases in addition to the index case. The findings suggest that the current full-course immunization has limited long-term effectiveness and is inefficient in preventing the transmission of MM among older children.

Governmental regulation induced pesticide retailers to provide more accurate advice on pesticide use to farmers in China.

BACKGROUND: In China, pesticide retailers have often been accused of providing inaccurate advice on pesticide use to farmers in a chaotic pesticide market. However, it is unclear whether governmental regulation of sales and advice on pesticide use by pesticide retailers induces them to provide accurate advice. RESULTS: Using survey data of 242 pesticide retailers in 2016, this study analyzes how pesticide retailers in China provide advice on pesticide use to farmers and examines whether governmental regulation induces pesticide retailers to provide accurate advice. The surveyed retailers were found to advise farmers to use the correct active ingredients in only 75.6% of observations. Retailers recommended pesticide application rates higher than the scientifically recommended levels among 57.2% of observations. The bivariate probit model estimation results show that highly intensive governmental regulation increases the probability of correct advice on pesticide use of pesticide retailers in the county and township seats by 13% and 19%, respectively. Moreover, highly intensive regulation can also increase the probability of pesticide non-overuse advice by the retailers from the retailers in the villages by 38%. CONCLUSION: Highly intensive governmental regulation can induce pesticide retailers to provide more accurate advice on pesticide use to farmers, but the effects differ across the locations of pesticide retailers. © 2021 Society of Chemical Industry.

Quantifying high-resolution spatial variations and local source impacts of urban ultrafine particle concentrations.

To quantify the fine-scale spatial variations and local source impacts of urban ultrafine particle (UFP) concentrations, we conducted 3-6 weeks of continuous measurements of particle number (a proxy for UFP) and other air pollutant (CO, NO2, and PM2.5) concentrations at 32 sites in Pittsburgh, Pennsylvania during the winters of 2017 and 2018. Sites were selected to span a range of urban land use attributes, including urban background, near local and arterial roads, traffic intersections, urban street canyon, near-highway, near large industrial source, and restaurant density. The spatial variations in urban particle number concentrations varied by about a factor of three. Particle number concentrations are 2-3 times more spatially heterogeneous than PM2.5 mass. The observed order of spatial heterogeneity is UFP > NO2 > CO > PM2.5. On average, particle number concentrations near local roads with a cluster of restaurants and near arterial roads are roughly two times higher than the urban background. Particle number concentrations in the urban street canyon, downwind of a major highway, and near large industrial sources are 2-4 times higher than background concentrations. While traffic is known as an important contributor to particle number concentrations, restaurants and industrial emissions also contribute significantly to spatial variations in Pittsburgh. Particle size distribution measurements using a mobile laboratory show that the local spatial variations in particle number concentrations are dictated by concentrations of particles smaller than 50 nm. A large fraction of urban residents (e.g., ~50%) in Pittsburgh live near local sources and are therefore exposed to 50%-300% higher particle number concentrations than urban background location. These locally emitted particles may have greater health effects than background particles.