Unrecognized risk of perfluorooctane sulfonate in promoting conjugative transfers of bacterial antibiotic resistance genes.

Antibiotic resistance is a major global health crisis facing humanity, with horizontal gene transfer (HGT) as a principal dissemination mechanism in the natural and clinical environments. Perfluoroalkyl substances (PFASs) are emerging contaminants of global concern due to their high persistence in the environment and adverse effects on humans. However, it is unknown whether PFASs affect the HGT of bacterial antibiotic resistance. Using a genetically engineered Escherichia coli MG1655 as the donor of plasmid-encoded antibiotic resistance genes (ARGs), E. coli J53 and soil bacterial community as two different recipients, this study demonstrated that the conjugation frequency of ARGs between two E. coli strains was (1.45 ± 0.17) × 10-5 and perfluorooctane sulfonate (PFOS) at environmentally relevant concentrations (2-50 µg L-1) increased conjugation transfer between E. coli strains by up to 3.25-fold. Increases in reactive oxygen species production, cell membrane permeability, biofilm formation capacity, and cell contact in two E. coli strains were proposed as major promotion mechanisms from PFOS exposure. Weighted gene co-expression network analysis of transcriptome data identified a series of candidate genes whose expression changes could contribute to the increase in conjugation transfer induced by PFOS. Furthermore, PFOS also generally increased the ARG transfer into the studied soil bacterial community, although the uptake ability of different community members of the plasmid either increased or decreased upon PFOS exposure depending on specific bacterial taxa. Overall, this study reveals an unrecognized risk of PFOS in accelerating the dissemination of antibiotic resistance. IMPORTANCE Perfluoroalkyl substances (PFASs) are emerging contaminants of global concern due to their high persistence in the environment and adverse health effects. Although the influence of environmental pollutants on the spread of antibiotic resistance, one of the biggest threats to global health, has attracted increasing attention in recent years, it is unknown whether environmental residues of PFASs affect the dissemination of bacterial antibiotic resistance. Considering PFASs, often called "forever" compounds, have significantly higher environmental persistence than most emerging organic contaminants, exploring the effect of PFASs on the spread of antibiotic resistance is more environmentally relevant and has essential ecological and health significance. By systematically examining the influence of perfluorooctane sulfonate on the antibiotic resistance gene conjugative transfer, not only at the single-strain level but also at the community level, this study has uncovered an unrecognized risk of PFASs in promoting conjugative transfers of bacterial antibiotic resistance genes, which could be incorporated into the risk assessment framework of PFASs.

Uptake of the Plant Agriculture-Used Antibiotics Oxytetracycline and Streptomycin by Cherry Radish─Effect on Plant Microbiome and the Potential Health Risk.

Antibiotics are used to control certain bacterial diseases in plant agriculture. Understanding antibiotic uptake by edible vegetables after application and associated risks on plant microbiome and human health is critical. In this study, oxytetracycline and streptomycin, the two most commonly used antibiotics in plant agriculture, were applied to cherry radish via continuous soil drenching to study their translocations into plant tissues, influence on radish microbiome, and the potential health risk to mice. The results demonstrated that oxytetracycline induced hormesis in radish plants and both antibiotics were translocated into the leaves, fruits, and roots of radishes from the soil, with significantly higher plant uptake of streptomycin than oxytetracycline. Interestingly, the proportion of culturable oxytetracycline or streptomycin-resistant bacteria in the antibiotic-accumulated radish tissues was significantly higher than that in the antibiotic-free radish tissues, although both bacterial and fungal communities in different radish tissues were not affected by the accumulated antibiotics, demonstrating that antibiotic application could enrich antibiotic resistance in the plant microbiome. Feeding mice with antibiotics-accumulated radish tissues did not show significant effects on the weight and blood glucose levels of mice. Overall, this study provides important insights into the risk of using antibiotics in plant agriculture.

Unraveling the influence of human fecal pollution on antibiotic resistance gene levels in different receiving water bodies using crAssphage indicator gene.

Discharged wastewater treatment plant (WWTP) effluents can contaminate receiving water bodies with human feces and alter the abundance of antibiotic resistance genes (ARGs). In this study, we examined the co-occurrence of ARGs, human fecal pollution indicator crAssphage, and antibiotics in human feces and a series of connected receiving water bodies affected by human feces, including water from different treatment units of a WWTP, river, lake, and tap waters. Results showed that crAssphage was detected in 68.2 % of the studied water bodies, confirming widespread human fecal contamination. Both ARG and crAssphage abundances exhibited a distance-decay effect from the emission source to the receiving environment. Interestingly, the detected ARG abundance in the water bodies was significantly correlated with crAssphage abundance but not with the residual antibiotic concentration, demonstrating that the presence of ARG could largely be explained by the extent of fecal pollution, with no clear signs of antibiotic selection. In addition, 14 ARGs co-shared by human feces and water bodies were significantly correlated with crAssphage. Furthermore, a close evolutionary relationship was observed between the blaTEM-1 gene from human feces and aquatic environments. These results imply a potential ARG exchange between human feces and receiving water bodies. Overall, this study provides important insights into the distribution and sources of ARGs in water bodies affected by human fecal contamination.

NaCl salinity enhances tetracycline bioavailability to Escherichia coli on agar surfaces.

Soil salinity is a worldwide problem and is damaging soil functions. Meanwhile, increasing amounts of anthropogenic antibiotics are discharged to agricultural soils. Little is known about how soil salinity (e.g., NaCl) could influence the bioavailability of antibiotics to bacteria. In this study, a tetracycline-responsive Escherichia coli bioreporter grew on the surfaces of agar microcosms at the same tetracycline concentration (200 µg/L), but various NaCl concentrations (0.5-19.2 g/L) with estimated osmotic potential of -0.18 to -1.80 MPa, and agar content (0.3%-5%) with estimated intrinsic permeability of 38 to 32,928 nm2. These agar microcosms mimicked very fine textured soils with a range of NaCl salinity. Increasing agar content lowered the intrinsic permeability hence decreasing tetracycline bioavailability to E. coli, due likely to the reduced mass transfer of tetracycline via water flow. Intriguingly, tetracycline bioavailability increased with increasing NaCl concentration which caused the increase in osmotic stress. This is contradictory to the notion that osmotic stress reduces bacterial chemical uptake. Further analysis of E. coli membrane integrity demonstrated that the enhanced tetracycline bioavailability to bacteria could result from the compromised cell membranes and enhanced membrane permeability at higher NaCl salinity. Overall, this study suggests that high soil salinity (NaCl) may enhance the selection pressure exerted by antibiotics on bacteria.

Assessment of structural brain changes in patients with type 2 diabetes mellitus using the MRI-based brain atrophy and lesion index.

Patients with type 2 diabetes mellitus (T2DM) often have cognitive impairment and structural brain abnormalities. The magnetic resonance imaging (MRI)-based brain atrophy and lesion index can be used to evaluate common brain changes and their correlation with cognitive function, and can therefore also be used to reflect whole-brain structural changes related to T2DM. A total of 136 participants (64 men and 72 women, aged 55-86 years) were recruited for our study between January 2014 and December 2016. All participants underwent MRI and Mini-Mental State Examination assessment (including 42 healthy control, 38 T2DM without cognitive impairment, 26 with cognitive impairment but without T2DM, and 30 T2DM with cognitive impairment participants). The total and sub-category brain atrophy and lesion index scores in patients with T2DM with cognitive impairment were higher than those in healthy controls. Differences in the brain atrophy and lesion index of gray matter lesions and subcortical dilated perivascular spaces were found between non-T2DM patients with cognitive impairment and patients with T2DM and cognitive impairment. After adjusting for age, the brain atrophy and lesion index retained its capacity to identify patients with T2DM with cognitive impairment. These findings suggest that the brain atrophy and lesion index, based on T1-weighted and T2-weighted imaging, is of clinical value for identifying patients with T2DM and cognitive impairment. Gray matter lesions and subcortical dilated perivascular spaces may be potential diagnostic markers of T2DM that is complicated by cognitive impairment. This study was approved by the Medical Ethics Committee of University of South China (approval No. USC20131109003) on November 9, 2013, and was retrospectively registered with the Chinese Clinical Trial Registry (registration No. ChiCTR1900024150) on June 27, 2019.

Halide salts induced the photodegradation of a fat-burning compound 2, 4-dinitrophenol by iron-montmorillonite.

Natural montmorillonite clay and anthropogenic organic pollutants frequently coexist in the estuarine environment where freshwater from rivers mixes with saltwater from the ocean. In this environment, the sharply changed aqueous chemistry especially salt content could significantly alter the photochemical behaviors of pollutants. However, this process was rarely investigated. In this study, the photodegradation of a representative anthropogenic weight-loss compound 2,4-dinitrophenol in the presence of Fe3+-montmorillonite and different halide salts was systematically investigated. Results show that 2,4-dinitrophenol was resistant to photodegradation by Fe3+-montmorillonite alone, but the presence of NaCl, NaBr, and sea salts in the system can evoke significant 2,4-dinitrophenol degradation. The enhancement effect was further elucidated as the replacement reaction between the clay associated Fe3+ and Na + which leads to the release of more interlayer Fe3+ from montmorillonite, resulting in increased production of high active hydroxyl radicals (˙OH) that can substantially damage 2,4-dinitrophenol molecule. In addition, halogen radicals from the reaction of halide ions with ˙OH were also confirmed to participate in 2,4-dinitrophenol degradation. Overall, this study implied that the changed salty condition in the estuarine water could induce the rapid transformation of organic pollutants that move from freshwater and have relatively stable photochemical properties.

Correlation Between Tumor Location and Clinical Properties of Glioblastomas in Frontal and Temporal Lobes.

BACKGROUND: Tumor location is a major prognostic factor in glioblastomas and may be associated with clinical properties. This study established and analyzed the correlation between tumor location and clinical properties of glioblastomas in frontal and temporal lobes. METHODS: This retrospective study determined the location of glioblastomas in the frontal lobe (FL) or temporal lobe (TL) based on preoperative magnetic resonance imaging. Clinical, radiologic, and molecular characteristics of FL and TL glioblastomas were compared to define their clinical properties, including sex, age, sides, relationship to ventricle, imaging subtypes, volume, isocitrate dehydrogenase mutation, promoter methylation of O6-methylguanine-DNA methyltransferase, progression-free survival, and overall survival. RESULTS: The study enrolled 406 patients (182 [44.83%] in FL group and 224 [55.17%] in TL group) with a mean age of 69.8 years. Compared with FL group, TL group had higher incidence of female patients (P = 0.024), tumor location distant to the ventricle (P = 0.006), isocitrate dehydrogenase mutations (P = 0.021), promoter methylation of O6-methylguanine-DNA methyltransferase (P = 0.012), and prolonged progression-free survival and overall survival (P < 0.05). No significant differences were observed between groups with respect to age ≥60 years at study entry (P = 0.668), sides (P = 0.879), imaging subtypes (P = 0.362), or volume (P = 0.709). CONCLUSIONS: This study demonstrated that different tumor locations are associated with diverse clinical properties of glioblastomas in FL and TL. This information will aid in increasing understanding of glioblastoma biology for application in baseline comparisons in future clinical trials.

Choice for the removal of bloody cerebrospinal fluid in postcoiling aneurysmal subarachnoid hemorrhage: external ventricular drainage or lumbar drainage?

AIM: External ventricular drainage (EVD) and lumbar drainage (LD) are the most widely used procedures for continued bloody cerebrospinal fluid drainage. Each has his own advantages and disadvantages. Here, we compared complications and clinical outcomes in patients with World Federation of Neurosurgical Societies (WFNS) grade III aneurysmal subarachnoid hemorrhage (aSAH) who underwent coil placement followed by EVD or LD. MATERIAL AND METHODS: In this prospective, controlled study, all patients with aSAH classified as WFNS grade III who underwent coil placement at our institution were divided randomly into 2 groups: the EVD group and the LD group. The ratios of intracerebral hemorrhage, vasospasm, infection, duration of catheter placement, hydrocephalus, and Glasgow outcome scale (GOS) after 2 months of onset were analyzed between the 2 groups. RESULTS: A total of 148 patients (mean age 56.8 years) were enrolled in this study. Seventy-six patients were assigned to the EVD group, and 72 patients were assigned to the LD group. The average time interval from stroke onset to surgery was 35.1 h. Compared with the EVD group, the LD group had a lower incidence of intracerebral hemorrhage, slightly higher rates of infection and hydrocephalus, and similar vasospasm and chronic hydrocephalus rates, durations of catheter placement, and GOS scores at 2 months after onset. CONCLUSION: In order to improve the clinical outcomes of patients with aSAH, we suggest that LD is better than EVD for patients with WFNS grade III aSAH who underwent coil placement.

Analysis of related factors affecting prognosis of shunt surgery in patients with secondary normal pressure hydrocephalus.

OBJECTIVE: The management of secondary normal pressure hydrocephalus (sNPH) is controversial. Many factors may affect the surgery effect. The purpose of this study was to identify the possible factors influencing prognosis and provide theoretical basis for clinical treatment of sNPH. METHODS: A retrospective study was carried out to investigate the results of 31 patients with sNPH who underwent ventriculoperitoneal shunt surgery from January 2007 to December 2011. We processed the potential influencing factors by univariate analysis and the result further by multivariate logistic regression analysis. RESULTS: Factors including age, disease duration and Glasgow coma scale (GCS) score before surgery significantly influenced the prognosis of sNPH (P less than 0.05). Further logistic regression analysis showed that all the three factors are independent influencing factors. CONCLUSION: Age, disease duration and GCS score before surgery have positive predictive value in estimating favorable response to surgical treatment for sNPH.

Influence of acute ethanol intoxication on neuronal apoptosis and Bcl-2 protein expression after severe traumatic brain injury in rats.

OBJECTIVE: To study the influence and mechanism of acute ethanol intoxication (AEI) on rat neuronal apoptosis after severe traumatic brain injury (TBI). METHODS: Ninety-six Sprague-Dawley rats were randomly divided into four groups: normal control, AEI-only, TBI-only and TBI+AEI (n equal to 24 for each). Severe TBI model was developed according to Feeney's method. Rats in TBI+AEI group were firstly subjected to AEI, and then suffered head trauma. In each group, animals were sacrificed at 6 h, 24 h, 72 h, and 168 h after TBI. The level of neuronal apoptosis and the expression of Bcl-2 protein were determined by TUNEL assay and immunohistochemical method, respectively. RESULTS: Apoptotic cells mainly distributed in the cortex and white matter around the damaged area. Neuronal apoptosis significantly increased at 6 h after trauma and peaked at 72 h. Both the level of neuronal apoptosis and expression of Bcl-2 protein in TBI-only group and TBI+AEI group were higher than those in control group (P less than 0.05). Compared with TBI-only group, the two indexes were much higher in TBI+AEI group at all time points (P less than 0.05). CONCLUSION: Our findings suggest that AEI can increase neuronal apoptosis after severe TBI.

Zero drift of intraventricular and subdural intracranial pressure monitoring systems.

OBJECTIVE: To assess zero drift of intraventricular and subdural intracranial pressure (ICP) monitoring systems. METHODS: A prospective study was conducted in patients who received Codman ICP monitoring in the neurosurgical department from January 2010 to December 2011. According to the location of sensors, the patients were categorized into two groups: intraventricular group and subdural group. Zero drift between the two groups and its association with the duration of ICP monitor were analyzed. RESULTS: Totally, 22 patients undergoing intraventricular ICP monitoring and 27 receiving subdural ICP monitoring were enrolled. There was no significant difference in duration of ICP monitoring, zero drift value and its absolute value between intraventricular and subdural groups (5.38 d+/-2.58 d vs 4.58 d+/-2.24 d, 0.77 mm Hg+/-2.18 mm Hg vs 1.03 mm Hg+/-2.06 mm Hg, 1.68 mm Hg+/-1.55 mm Hg vs 1.70 mm Hg+/-1.53 mm Hg, respectively; all P larger than 0.05). Absolute value of zero drift in both groups significantly rose with the increased duration of ICP monitoring (P less than 0.05) while zero drift value did not. Moreover, daily absolute value in the intraventricular group was significantly smaller than that in the subdural group (0.27 mm Hg+/-0.32 mm Hg vs 0.29 mm Hg+/-0.18 mm Hg, P less than 0.05). CONCLUSION: This study demonstrates that absolute value of zero drift significantly correlates with duration of both intraventricular and subdural ICP monitoring. Due to the smaller daily absolute value, ICP values recorded from intraventricular system may be more reliable than those from subdural system.

Which side of lateral ventricles to choose during external ventricular drainage in patients with intraventricular hemorrhage: ipsilateral or contralateral?

BACKGROUND: We attempted to investigate the effect of external ventricular drainage (EVD) plus intraventricular fibrinolysis from ipsilateral or contralateral ventricle on clinical outcomes in patients with intraventricular hemorrhage. METHODS: We undertook a prospective controlled study. Patients with acute obstructive hydrocephalus after intraventricular hemorrhage were randomized to receive EVD from ipsilateral ventricle (ipsilateral group [IG]) or contralateral ventricle (contralateral group [CG]). They received intracranial pressure (ICP) monitoring and intraventricular injection of urokinase after surgery. We compared clinical outcomes and complications between groups. RESULTS: A total of 45 patients were enrolled, with a mean age of 55.4 years. We assigned 28 patients assigned to the IG and 17 patients to the CG. Patients in the IG showed significantly faster clot clearance in the third and fourth ventricles on computed tomography than those in the CG (3.3 ± 1.0 d versus 3.9 ± 0.8 d; P = 0.042). Analysis of ICP data showed that initial ICP in the IG was significantly higher than in the CG (20.4 ± 7.2 mm Hg versus 16.5 ± 4.4 mm Hg; P = 0.039), as was the average daily ICP on the following 3 d. The percentage of ICP readings over 20 mm Hg in the IG was also significantly larger than that in the CG (18.0% versus 10.9%; P < 0.001). There was no significant difference in the incidence of complications regarding rebleeding, infection, epilepsy, or communicating hydrocephalus. Neither 30-d mortality rate nor Glasgow Outcome Scale score revealed significant differences between the two groups. CONCLUSIONS: External ventricular drainage plus EVT from the ipsilateral or contralateral ventricle has similar short-term outcomes and complications in patients with intraventricular hemorrhage. Faster clot clearance in the third and fourth ventricles but higher ICP levels at the early stage may be expected in patients with EVD from the ipsilateral ventricle, compared with those from with EVD from the contralateral ventricle.

Application of ulinastatin in severe craniocerebral injuries.

OBJECTIVE: To assess the therapeutic effect of ulinastatin on severe craniocerebral injuries and to explore its mechanism. METHODS: There were 87 cases of severe brain injury in this series and they were either treated by ulinastatin (treatment group, 41 cases) or not (control group, 46 cases) besides routine managements. We estimated C-reactive protein, interleukin-6, superoxide dismutase, and endothelin from plasmas of all the cases on the 1st, 3rd, 5th, and 7th day after injury. RESULTS: C-reactive protein level rose on the 1st and 3rd day after injury in the two groups, but descended in treatment group on the 5th and 7th day and was significantly lower than that in control group (P < 0.01). No significant difference was found for interleukin-6 in two groups during 1-5 days after injury, but on the 7th day, it decreased significantly in treatment group than control one (P < 0.01). Superoxide dismutase was higher in treatment group than control one in 5-7 days after injury (P < 0.01). Endothelin elevated on the 1st day after injury but dropped afterwards in the two groups, in which the level in treatment group was lower than that in control one. The incidence of gastrointestinal hemorrhage was lower in treatment group than control one (P < 0.01). CONCLUSIONS: Ulinastatin has the function of protecting cerebral tissue, reducing the incidence of gastrointestinal hemorrhage, improving hepatic and renal function and prognosis.