Machine learning reveals the selection pressure exerted by nonantibiotic pharmaceuticals at environmentally relevant concentrations on antibiotic resistance genotypes.

The emergence and increasing prevalence of antibiotic resistance pose a global public risk for human health, and nonantimicrobial pharmaceuticals play an important role in this process. Herein, five nonantimicrobial pharmaceuticals, including acetaminophen (ACT), clofibric acid (CA), carbamazepine (CBZ), caffeine (CF) and nicotine (NCT), tetracycline-resistant strains, five ARGs (sul1, sul2, tetG, tetM and tetW) and one integrase gene (intI1), were detected in 101 wastewater samples during two typical sewage treatment processes including anaerobic-oxic (A/O) and biological aerated filter (BAF) in Harbin, China. The impact of nonantibiotic pharmaceuticals at environmentally relevant concentrations on both the resistance genotypes and resistance phenotypes were explored. The results showed that a significant impact of nonantibiotic pharmaceuticals at environmentally relevant concentrations on tetracycline resistance genes encoding ribosomal protection proteins (RPPs) was found, while no changes in antibiotic phenotypes, such as minimal inhibitory concentrations (MICs), were observed. Machine learning was applied to further sort out the contribution of nonantibiotic pharmaceuticals at environmentally relevant concentrations to different ARG subtypes. The highest contribution and correlation were found at concentrations of 1400-1800 ng/L for NCT, 900-1500 ng/L for ACT and 7000-10,000 ng/L for CF for tetracycline resistance genes encoding RPPs, while no significant correlation was found between the target compounds and ARGs when their concentrations were lower than 500 ng/L for NCT, 100 ng/L for ACT and 1000 ng/L for CF, which were higher than the concentrations detected in effluent samples. Therefore, the removal of nonantibiotic pharmaceuticals in WWTPs can reduce their selection pressure for resistance genes in wastewater.

Development and validation of a nomogram to predict the recurrence of eyelid sebaceous gland carcinoma.

PURPOSE: Eyelid sebaceous gland carcinoma (SGC) is a malignancy with fatal risk, high recurrence rate, and pagetoid spread. Thus, recurrence risk prediction and prompt treatment are extremely important. This study aimed to develop a nomogram to predict SGC recurrence based on potential risk factors. METHODS: We conducted a retrospective study to train and test a nomogram based on the clinical data of 391 patients across our hospital (304) and other grass-roots hospitals (87). After Cox regression, predictors included in the nomogram were selected, and sensitivity, specificity, concordance index (C-index), etc., were calculated to test their discrimination ability. RESULTS: After a median follow-up period of 4.12 years, SGC recurred in 52 (17.11%) patients. The 1-, 2-, and 5-year recurrence-free survival rates were 88.3%, 85.4%, and 81.6%, respectively. We examined five risk factors, such as lymph node metastasis at initial diagnosis (hazard ratio [HR], 2.260; 95% confidence interval [CI], 1.021-5.007), Ki67 (HR, 1.036; 95% CI, 1.020-1.052), histology differentiation degree (HR, 2.274; 95% CI, 1.063-4.865), conjunctival pagetoid infiltration (HR, 2.100; 95% CI, 1.0058-4.167), and orbital involvement (HR, 4.764; 95% CI, 1.436-15.803). The model had good discrimination in both internal and external test sets. The model had good discrimination in both internal and external test sets. The sensitivity of the internal test and external test set were 0.722 and 0.806, respectively, and specificity of the internal test and external test set were 0.886 and 0.893, respectively. CONCLUSION: We examined the potential risk factors for eyelid SGC recurrence and constructed a nomogram, which complements the TNM system in terms of prediction, indicating that our nomogram has the potential to reach clinical significance. This nomogram has the potential to assist healthcare practitioners in promptly detecting patients who are at an elevated risk and in tailoring clinical interventions to meet their individualized needs.

Outcomes of Patients With Dysthyroid Optic Neuropathy Treated With Intravenous Corticosteroids and/or Orbital Decompression Surgery: A Systematic Review and Meta-analysis.

CONTEXT: The level of evidence is low for the treatment of patients with dysthyroid optic neuropathy (DON) and there is no consensus on the treatment of DON with intravenous high-dose glucocorticoids (ivGC) or direct surgical decompression. OBJECTIVE: To compare the efficacy of glucocorticoid treatment and orbital decompression (OD) in DON. DATA SOURCES: PubMed, EMBASE, and Cochrane Library were searched along with other sources. STUDY SELECTION: A total of 17 studies met the inclusion criteria. DATA EXTRACTION: Standard methodological guidance of the Cochrane Handbook was used and data were independently extracted by multiple observers. The primary outcomes were the improvement of best corrected visual acuity (ΔBCVA). Secondary outcomes were proptosis reduction, change in diplopia, visual field defects, and intraocular pressure (IOP). DATA SYNTHESIS: The ΔBCVA in the ivGC + OD group was improved 0.26 LogMAR more than in the ivGC group (P = .007). The ΔBCVA in the OD group was better than in the ivGC group (P = .008). Posttreatment proptosis in the ivGC + OD and OD groups were improved further by 3.54 mm and 3.00 mm, respectively, than in the ivGC group (P < .01). The mean deviation (MD) in the ivGC + OD group was improved by an additional 5.33 dB than in the ivGC group (P = .002). The IOP in the ivGC + OD group was improved further than in the ivGC group (P = .03). CONCLUSIONS: Based on the results of the present meta-analysis, OD or ivGC + OD may be more effective in improving BCVA and MD and reducing proptosis compared with ivGC. Compared with ivGC alone, ivGC + OD is more effective in improving IOP than ivGC. Although this study improves the hierarchy of evidence in the treatment of DON, additional randomized controlled trials are needed to confirm this conclusion.

Occurrence, distribution, and risk assessment of quinolone antibiotics in municipal sewage sludges throughout China.

A nationwide study of the occurrence, distribution, potential drivers, and ecological risks of 24 quinolone antibiotics (QNs) in 74 Chinese sludge samples from 48 wastewater treatment plants (WWTPs) was conducted. In domestic sludge, the ∑QNs concentrations were  3rd-generation QNs > 4th-generation QNs > 1st-generation QNs. Meanwhile, abundant veterinary and human/veterinary quinolones (

The role of liver kinase B1 in tumor progression through regulation of lipid metabolism

The somatic mutation of liver kinase B1 (LKB1) has been implicated in various tumors, which is reflected in the survival, proliferation, and metastasis of tumor cells. However, the regulation of LKB1 in lipid metabolism, a process that is involved in tumor progression is not completely clear. We conclude that LKB1 deficiency results in abnormal expression and activation of multiple molecules related to lipid metabolism which locate downstream of AMP-activated protein kinase (AMPK) or salt-induced kinase (SIK). Abnormal lipid metabolism induced by LKB1 deficiency contributes to the proliferation and metastasis of tumor cells through energy regulation. (AU)

The role of liver kinase B1 in tumor progression through regulation of lipid metabolism.

The somatic mutation of liver kinase B1 (LKB1) has been implicated in various tumors, which is reflected in the survival, proliferation, and metastasis of tumor cells. However, the regulation of LKB1 in lipid metabolism, a process that is involved in tumor progression is not completely clear. We conclude that LKB1 deficiency results in abnormal expression and activation of multiple molecules related to lipid metabolism which locate downstream of AMP-activated protein kinase (AMPK) or salt-induced kinase (SIK). Abnormal lipid metabolism induced by LKB1 deficiency contributes to the proliferation and metastasis of tumor cells through energy regulation.

Changes in antibiotic resistance genotypes and phenotypes after two typical sewage disposal processes.

Antibiotic resistome is a growing concern around the world. Wastewater treatment plants (WWTPs) have been identified as hotspots for antibiotic resistance gene (ARG) research. However, the distribution of antibiotic resistance genotypes and phenotypes in biofilm wastewater treatment system is poorly understood. In this study, the abundance and fate of antibiotic resistance genotypes and phenotypes in two typical wastewater treatment processes [biological aerated filter (BAF), anaerobic-oxic (A/O)] were quantitatively studied. The average removal rate of total ARGs was greater than 90%. In the biological treatment unit, the abundance of ARGs increased in the A/O unit and decreased in the biofilm unit. In addition, the resistance of tetracycline resistant bacteria changed after sewage disposal, which was closely related to the evolution of bacterial community. In total, the removal rate of resistance bacteria in A/O system was lower than that in BAF system. Genotypes were the basis of determining the phenotypes of microbial resistance. But it is necessary to pay close attention to antibiotic resistance phenotype due to its high variability. More specifically, antibiotic resistance mitigation in WWTPs should focus more on removing bacterial hosts to reduce the release of ARGs into the environment.

The spatiotemporal distribution and potential risk assessment of 19 phthalate acid esters in wastewater treatment plants in China.

The spatiotemporal distribution of phthalate acid esters (phthalates, PAEs) in wastewater treatment plants (WWTPs) in China was studied. The concentration of PAEs in influent and effluent increased from 2009 to 2016, indicating that the exposure level of PAEs in China increased continuously. Although the concentration of PAEs in sewage sludge in China ranged from 33.3 to 298 ug/g, there was no obvious spatial distribution pattern. Among the 19 PAE homologues, DEHP, DnBP, and DIBP were the most abundant phthalates detected in wastewater and sludge. Ecological risk assessment confirmed that there was a high chronic and acute risk of DIBP in effluent since 2015. Therefore, this study highlights the need for further studies on the exposure and toxicology of DIBP. Dietary intake accounted for more than 98% of the total risk, indicating that the risk of sludge application in agricultural land was much higher than that in nonagricultural land. The results from this study will provide valuable information for the safe disposal of sludge and wastewater.

Occurrence, distribution and human exposure of phthalic esters in road dust samples across China.

203 road dust samples were conducted across China covering 28 provinces from January to February，2016 to comprehensively investigates the occurrence, distribution and human exposure of 21 phthalic esters (PAEs). The concentration of Σ21PAEs in road dust ranged from 2.3 to 531 mg/kg, with a mean concentration of 64.1 ± 57.2 mg/kg. DEHP, DnBP and DiBP were the dominant components accounting for 63.3-97.9% (mean: 92.1%) of the Σ21PAEs. Significant Pearson correlation (r = 0.51, p < 0.0001) between Σ21PAEs concentrations and longitude demonstrated a distinguished geographical trend. Higher concentration of PAEs in sidewalk (SW) and trunk road (TR) may reflect influence of human activities such as shoe wear and traffic load. Significant differences were found among different human activities area (urban commercial, urban residential, and suburbs/rural). For total daily intake of Æ©21PAEs via street dust, children had the highest exposure risk followed by teenagers and adults with the median values of 160.8, 43.6, and 37.7 ng/kg-bw/day, respectively. The maximum exposure risk of PAEs calculated based on measurement and simulation were all far below reference values. The sensitivity analysis results demonstrated that concentrations, ingestion rate (IR) and fraction of PAEs absorbed in the skin (AF) were most important parameters on the assessment of exposure risk of PAEs via street dust. Specific parameters based on China and Chinses population is needed to obtain more reliable exposure risk via street dust.

Exploring the disparity of inhalable bacterial communities and antibiotic resistance genes between hazy days and non-hazy days in a cold megacity in Northeast China.

The physicochemical properties of inhalable particles during hazy days have been extensively studied, but their biological health threats have not been well-explored. This study aimed to explore the impacts of haze pollution on airborne bacteria and antibiotic-resistance genes (ARGs) by conducting a comparative study of the bacterial community structure and functions, pathogenic compositions, and ARGs between hazy days and non-hazy days in a cold megacity in Northeast China. The results suggested that bacterial communities were shaped by local weather and customs. In this study, cold-resistant and Chinese sauerkraut-related bacterial compositions were identified as predominant genera. In the comparative analysis, higher proportions of gram-negative bacteria and pathogens were detected on hazy days than on non-hazy days. Pollutants on hazy days provided more nutrients (sulfate, nitrate and ammonium) for bacterial metabolism but also caused more bacterial cell damage and death than on non-hazy days. This study also detected increases in the sub-types and average absolute abundance of airborne resistance genes on hazy days compared to non-hazy days. The results of this study revealed that particle pollution promotes the dissemination and exchange of pathogenic bacteria and ARGs among large urban populations, which leads to a higher potential for human inhalation exposure.