Soot nanoparticles promote ferroptosis in dopaminergic neurons via alteration of m6A RNA methylation in Parkinson's disease.

Soot nanoparticles (SNPs) are black carbon prevalent in atmospheric environment with significant impacts on public health, leading to neurodegenerative diseases including development of Parkinson's disease (PD). This study investigated the effects of SNPs exposure on PD symptoms, employing both in vivo and in vitro PD models. In the in vivo experiments, animal behavior assessments showed that SNPs exposure exacerbated motor and cognitive impairments in PD mice. Molecular biology techniques further unveiled that SNPs aggravated degeneration of dopaminergic neurons. In vitro experiments revealed that SNPs exposure intensified ferroptosis of PD cells by increasing reactive oxygen species and iron ion levels, while reducing glutathione levels and mitochondrial membrane potential. Sequencing tests indicated elevated N6-methyladenosine (m6A) alteration of the ferroptosis-related protein, acyl-CoA synthetase long chain family member 4 (ACSL4). This study demonstrates that SNPs may exacerbate the onset and progression of PD by recruiting YTH domain-containing family protein 1 (YTHDF1) protein, enhancing m6A methylation in the ACSL4 5'UTR, amplifying ACSL4 protein expression, and accelerating the ferroptosis process in dopaminergic neurons. These molecular mechanisms underlying SNPs exacerbation of PD development may provide crucial insights for formulating environmental safety regulations and potential therapeutic strategies addressing PD in populations residing in regions with varied air quality.

TREM2 Deficiency Aggravates NLRP3 Inflammasome Activation and Pyroptosis in MPTP-Induced Parkinson's Disease Mice and LPS-Induced BV2 Cells.

Microglia-mediated neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Triggering receptor expressed on myeloid cells 2 (TREM2) confers strong neuroprotective effects in PD by regulating the phenotype of microglia. Recent studies suggest that TREM2 regulates high glucose-induced microglial inflammation through the NLRP3 signaling pathway. This study aimed to investigate the effect of TREM2 on NLRP3 inflammasome activation and neuroinflammation in PD. Mice were injected with AAV-TREM2-shRNA into both sides of the substantia nigra using a stereotactic injection method, followed by intraperitoneal injection of MPTP to establish chronic PD mouse model. Behavioral assessments including the pole test and rotarod test were conducted to evaluate the effects of TREM2 deficiency on MPTP-induced motor dysfunction. Immunohistochemistry of TREM2 and tyrosine hydroxylase (TH), immunohistochemistry and immunofluorescence Iba1, Western blot of NLRP3 inflammasome and its downstream inflammatory factors IL-1ß and IL-18, and the key pyroptosis factors GSDMD and GSDMD-N were performed to explore the effect of TREM2 on NLRP3 inflammasome and neuroinflammation. In an in vitro experiment, lentivirus was used to interfere with the expression of TREM2 in BV2 microglia, and then lipopolysaccharide (LPS) and adenopterin nucleoside triphosphate (ATP) were used to stimulate inflammation to construct a cellular inflammation model. The expression differences of NLRP3 inflammasome and its components were detected by qPCR and Western blot. In vivo, TREM2 knockdown aggravated the loss of dopaminergic neuron and the decline of motor function. After TREM2 knockdown, the number of activated microglia was significantly increased, and the expression of cleaved caspase-1, NLRP3 inflammasome, IL-1ß, GSDMD, and GSDMD-N was increased. In vitro, TREM2 knockdown aggravated the inflammatory response of BV2 cells stimulated by LPS and promoted the activation of NLRP3 inflammasome through the NF-κB pathway. In addition, TREM2 knockdown also promoted the expression of TLR4/MyD88, an upstream factor of the NF-κB pathway. Our vivo and vitro data showed that TREM2 knockdown promoted NLRP3 inflammasome activation and downstream inflammatory response, promoted pyroptosis, and aggravated dopaminergic neuron loss. TREM2 acts as an anti-inflammatory in PD through the TLR4/MyD88/NF-κB pathway, which extends previous findings and supports the notion that TREM2 ameliorates neuroinflammation in PD.

Factors Associated with Return Visits by Elders within 72 Hours of Discharge from the Emergency Department.

Elders have a higher rate of return visits to the emergency department (ED) than other patients. It is critical to understand the risk factors for return visits to the ED by elders. The aim of this study was to determine the factors associated with return visits to the ED by elders. This study retrospectively reviewed the hospital charts of elders who returned to the ED within 72 h after discharge from ED. The risk factors identified in the Triage Risk Screening Tool were applied in this study. Of the elders discharged from the ED, 8.64% made a return visit to the ED within 72 h. The highest revisit rate occurred within 24 h after discharge. Factors associated with return ED visits within 24 h by elders were difficulty walking and having discharge care needs. The factor associated with ED return visits within 24-48 h was polypharmacy. Difficulty walking, having discharge care needs, and hospitalization within the past 120 days were associated with return visits made within 48-72 h following discharge. Identifying the reasons for return visits to the ED and providing a continuous review of geriatric assessment and discharge planning could reduce unnecessary revisits.

[Using Team Resource Management and Situational Simulation to Improve the Resuscitation Performance Completion Rate].

BACKGROUND & PROBLEMS: Cardiopulmonary resuscitation is an important issue in patient safety. After investigation, we identified the causes of the low rate of resuscitation completion in our emergency department as: incomplete utilization of available first-aid equipment, lack of standards related to task allocation, unclear moving line and instrument placement, lack of teamwork, and poor resuscitation-related communications during the COVID-19 pandemic. PURPOSE: The project aimed to improve the resuscitation performance completion rate. RESOLUTION: The project included designing equipment reminder cards and an airway car, designating specific responsibilities for each team member, establishing standard layouts and traffic flows, and providing situational simulation and team resource management training. RESULTS: After the intervention, the resuscitation performance completion rate had risen to 91.6% from the pre-intervention rate of 69.1%. This has since further risen to a relatively constant completion rate of 98.1%. CONCLUSIONS: The implementation of the team resource management and situational simulation training intervention in our ED improved both the resuscitation completion rate and the rate of return of spontaneous circulation (ROSC).

Increasing age- and gender-specific burden and complexity of multimorbidity in Taiwan, 2003-2013: a cross-sectional study based on nationwide claims data.

OBJECTIVE: Although there is accumulating evidence regarding multimorbidity in Western countries, this information is very limited in Asian countries. This study aimed to estimate population-based, age-specific and gender-specific prevalence and trends of multimorbidity in the Taiwanese population. DESIGN: This was a cross-sectional study based on claims data (National Health Insurance Research Database, Taiwan). PARTICIPANTS: The participants included a subset of the National Health Insurance Research Database, which contains claims data for two million randomly selected beneficiaries (~10% of the total population) under Taiwan's mandatory National Health Insurance system. OUTCOME MEASUREMENTS: The prevalence of multimorbidity in different age groups and in both sexes in 2003 and 2013 was reported. We analysed data on the prevalence of 20 common diseases in each age group and for both sexes. To investigate the clustering effect, we used graphical displays to analyse the likelihood of co-occurrence with one, two, three, and four or more other diseases for each selected disease in 2003 and 2013. RESULTS: The prevalence of multimorbidity (two or more diseases) was 20.07% in 2003 and 30.44% in 2013. In 2013, the prevalence varied between 5.21% in patients aged 20-29 years and 80.96% in those aged 80-89 years. In patients aged 50-79 years, the prevalence of multimorbidity was higher in women than in men. In men, the prevalence of chronic pulmonary disease and cardiovascular-related diseases was predominant, while in women the prevalence of osteoporosis, arthritis, cancer and psychosomatic disorders was predominant. Co-occurring diseases varied across different age and gender groups. CONCLUSIONS: The burden of multimorbidity is increasing and becoming more complex in Taiwan, and it was found to vary across different age and gender groups. Fulfilling the needs of individuals with multimorbidity requires collaborative work between healthcare providers and needs to take the age and gender disparities of multimorbidity into account.

Pooled analysis of nuclear acid sequence-based amplification for rapid diagnosis of Mycoplasma pneumoniae infection.

BACKGROUND: Mycoplasma pneumoniae (M pneumoniae) is a common human etiology of respiratory infections. Nuclear acid sequence-based amplification (NASBA) shows good value for the detection of M pneumoniae that surpasses PCR. However, the optimal detection technology still remains to be identified. The purpose of this meta-analysis was to systematically evaluate the overall accuracy of NASBA for diagnosing M pneumoniae infections. METHODS: The databases PubMed, Cochrane Library, Google Scholar, CNKI, Wang Fang, and Baidu Scholar were comprehensively searched from their initiation date to December 2017 for NASBA in the diagnosis of M pneumoniae infection. Meta-DiSc 1.4 statistical software was used to evaluate the sensitivity (SEN), specificity (SPE), negative likelihood ratio (-LR), positive likelihood ratio (+LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC). RevMan 5.2 statistical software was used for quality evaluation of the included articles. Publication bias was evaluated by funnel plot. RESULTS: Six articles with high quality, including 10 studies, were finally included in this meta-analysis. The combined statistics results for the diagnosis of M pneumoniae infection by NASBA were 0.77 (SEN, 95% CI: 0.71 to 0.82); 0.98 (SPE, 95% CI: 0.98 to 0.99); 0.22 (-LR, 95% CI: 0.13 to 0.39); 50.38 (+ LR, 95% CI: 21.85 to 116.17); 292.72 (DOR, 95% CI: 95.02 to 901.75); and 0.9875 (the area under the curve of SROC). CONCLUSION: Nuclear acid sequence-based amplification is a reliable technique to diagnose M pneumoniae infection. However, whether it can replace PCR and serology need to be further studied.

Ionic liquid-based dispersive liquid-liquid microextraction combined with functionalized magnetic nanoparticle solid-phase extraction for determination of industrial dyes in water.

N-butyl pyridinium bis((trifluoromethyl)sulfonyl)imide ([Hpy]NTf2) functionalized core/shell magnetic nanoparticles (MNPs, Fe3O4@SiO2@[Hpy]NTf2)) were prepared and applied as an adsorbent for magnetic solid phase extraction (MSPE) of three commonly used industrial dyes including malachite green, crystal violet and methylene blue. Extraction solution was mixed with 100 mg extraction material of Fe3O4@SiO2@[Hpy]NTf2, and 1 mL of acetonitrile was used to elute target analytes for further extraction and purification. [Hpy]NTf2 was used as extraction solution, and 500 µL methanol was selected as dispersive solvent in ionic liquid (IL) dispersive liquid-liquid microextraction (DLLME) method. After sonication for 5 min and centrifugation at 447 g for 10 min, 20 µL of sedimented phase was injected into HPLC-UV system. The limit of detection (LOD) and limit of quantification (LOQ) of current method were 0.03 and 0.16 µg·L-1, respectively, which indicated the sensitivity was comparable or even superior to other reported methods. The relative recoveries of the target analytes ranged from 86.1% to 100.3% with relative standard deviations between 0.3% and 4.5%. The developed method has been successfully applied to determine the level of three industrial dyes in different water samples.

Simultaneous determination of 12 pharmaceuticals in water samples by ultrasound-assisted dispersive liquid-liquid microextraction coupled with ultra-high performance liquid chromatography with tandem mass spectrometry.

A new analytical method was developed for simultaneous determination of 12 pharmaceuticals using ultrasound-assisted dispersive liquid-liquid microextraction (DLLME) followed by ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS). Six nonsteroidal anti-inflammatory drugs (NSAIDs, ketoprofen, mefenamic acid, tolfenamic acid, naproxen, sulindac, and piroxicam) and six antibiotics (tinidazole, cefuroxime axetil, ciprofloxacin, sulfamethoxazole, sulfadiazine, and chloramphenicol) were extracted by ultrasound-assisted DLLME using dichloromethane (800 µL) and methanol/acetonitrile (1:1, v/v, 1200 µL) as the extraction and dispersive solvents, respectively. The factors affecting the extraction efficiency, such as the type and volume of extraction and dispersive solvent, vortex and ultrasonic time, sample pH, and ionic strength, were optimized. The ultrasound-assisted process was applied to accelerate the formation of the fine cloudy solution by using a small volume of dispersive solvent, which increased the extraction efficiency and reduced the equilibrium time. Under the optimal conditions, the calibration curves showed good linearity in the range of 0.04-20 ng mL-1 (ciprofloxacin and sulfadiazine), 0.2-100 ng mL-1 (ketoprofen, tinidazole, cefuroxime axetil, naproxen, sulfamethoxazole, and sulindac), and 1-200 ng mL-1 (mefenamic acid, tolfenamic acid, piroxicam, and chloramphenicol). The LODs and LOQs of the method were in the range of 0.006-0.091 and 0.018-0.281 ng mL-1, respectively. The relative recoveries of the target analytes were in the range from 76.77 to 99.97 % with RSDs between 1.6 and 8.8 %. The developed method was successfully applied to the extraction and analysis of 12 pharmaceuticals in five kinds of water samples (drinking water, running water, river water, influent and effluent wastewater) with satisfactory results. Graphical Abstract Twelve pharmaceuticals in water samples analyted by UHPLC-MS/MS using ultrasound-assisted DLLME.

Solid-phase extraction combined with dispersive liquid-liquid microextraction and chiral liquid chromatography-tandem mass spectrometry for the simultaneous enantioselective determination of representative proton-pump inhibitors in water samples.

This report describes, for the first time, the simultaneous enantioselective determination of proton-pump inhibitors (PPIs-omeprazole, lansoprazole, pantoprazole, and rabeprazole) in environmental water matrices based on solid-phase extraction combined with dispersive liquid-liquid microextraction (SPE-DLLME) and chiral liquid chromatography-tandem mass spectrometry. The optimized results of SPE-DLLME were obtained with PEP-2 column using methanol-acetonitrile (1/1, v/v) as elution solvent, dichloroethane, and acetonitrile as extractant and disperser solvent, respectively. The separation and determination were performed using reversed-phase chromatography on a cellulose chiral stationary phase, a Chiralpak IC (250 mm × 4.6 mm, 5 µm) column, under isocratic conditions at 0.6 mL min(-1) flow rate. The analytes were detected in multiple reaction monitoring (MRM) mode by triple quadrupole mass spectrometry. Isotopically labeled internal standards were used to compensate matrix interferences. The method provided enrichment factors of around 500. Under optimal conditions, the mean recoveries for all eight enantiomers from the water samples were 89.3-107.3 % with 0.9-10.3 % intra-day RSD and 2.3-8.1 % inter-day RSD at 20 and 100 ng L(-1) levels. Correlation coefficients (r (2)) ≥ 0.999 were achieved for all enantiomers within the range of 2-500 µg L(-1). The method detection and quantification limits were at very low levels, within the range of 0.67-2.29 ng L(-1) and 2.54-8.68 ng L(-1), respectively. This method was successfully applied to the determination of the concentrations and enantiomeric fractions of the targeted analytes in wastewater and river water, making it applicable to the assessment of the enantiomeric fate of PPIs in the environment. Graphical Abstract Simultaneous enantioselective determination of representative proton-pump inhibitors in water samples.

A combined experimental/computational study on metal-organic framework MIL-101(Cr) as a SPE sorbent for the determination of sulphonamides in environmental water samples coupling with UPLC-MS/MS.

As a novel kind of materials, metal-organic frameworks (MOFs) have great potential for the preconcentration of trace analytes. In our work, MIL-101(Cr) was prepared and applied as a solid phase extraction (SPE) sorbent for the pretreatment of sulfadiazine (SDA), sulfamethazine (SMZ), sulfachloropyridazine (SCP) and sulfamethoxazole (SMX) in different environmental water samples coupling with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detection. Experimental parameters, such as SPE materials, pH of water sample, volume of sample, flow rate, and type and volume of elution solvent, were properly optimized. Under the optimum conditions, good sensitivity levels were achieved with the detection limits of 0.03-0.08µg/L and the quantitation limits of 0.11-0.27µg/L. The linear ranges were from 0.2-40 or 0.5-100µg/L (r(2)>0.996) for the analytes, and the relative recoveries were in the range from 83.5% to 107.3% with the relative standard deviations (RSD) between 0.2% and 8.0% (n=6). In addition, computational simulation was primarily used to predict the adsorption of MIL-101(Cr) toward sulphonamides (SAs), and also demonstrated the molecular interactions and free binding energies with the molecular modeling method. The results revealed that the combination of experimental and computational study not only accurately recognized the adsorption of MIL-101(Cr) on SAs, but also provided a new strategy on the trace contaminant analysis.

Solid-phase extraction in combination with dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography-tandem mass spectrometry analysis: the ultra-trace determination of 10 antibiotics in water samples.

A novel method, solid-phase extraction combined with dispersive liquid-liquid microextraction (SPE-DLLME), was developed for ultra-preconcentration of 10 antibiotics in different environmental water samples prior to ultra-high performance liquid chromatography-tandem mass spectrometry detection. The optimized results were obtained as follows: after being adjusted to pH 4.0, the water sample was firstly passed through PEP-2 column at 10 mL min(-1), and then methanol was used to elute the target analytes for the following steps. Dichloromethane was selected as extraction solvent, and methanol/acetonitrile (1:1, v/v) as dispersive solvent. Under optimal conditions, the calibration curves were linear in the range of 1-1000 ng mL(-1) (sulfamethoxazole, cefuroxime axetil), 5-1000 ng mL(-1) (tinidazole), 10-1000 ng mL(-1) (chloramphenicol), 2-1000 ng mL(-1) (levofloxacin oxytetracycline, doxycycline, tetracycline, and ciprofloxacin) and 1-400 ng mL(-1) (sulfadiazine) with a good precision. The LOD and LOQ of the method were at very low levels, below 1.67 and 5.57 ng mL(-1), respectively. The relative recoveries of the target analytes were in the range from 64.16% to 99.80% with relative standard deviations between 0.7 and 8.4%. The matrix effect of this method showed a great decrease compared with solid-phase extraction and a significant value of enrichment factor (EF) compared with dispersive liquid-liquid microextraction. The developed method was successfully applied to the extraction and analysis of antibiotics in different water samples with satisfactory results.

Trace determination of antibacterial pharmaceuticals in fishes by microwave-assisted extraction and solid-phase purification combined with dispersive liquid-liquid microextraction followed by ultra-high performance liquid chromatography-tandem mass spectrometry.

A novel pretreatment method involving microwave-assisted extraction and solid-phase purification combined with dispersive liquid-liquid microextraction (MAE-SPP-DLLME) followed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was established for the simultaneous determination of six antibacterial pharmaceuticals including metronidazole, tinidazole, chloramphenicol, thiamphenicol, malachite green and crystal violet. The conditions of MAE were optimized using an orthogonal design and the optimal conditions were found to be 8mL for acetonitrile, 50°C for 5min. Then, neutral alumina column was employed in the solid-phase purification. Finally, the critical parameters affecting DLLME, including selection of extraction and dispersive solvent, adjustment of pH, salt concentration, extraction time, were investigated by single factor study. Under optimum conditions, good linearities (r>0.9991) and satisfied recoveries (Recoveries>87.0%, relative standard deviation (RSD)<6.3%) were observed for all of the target analytes. The limits of detection and quantification were 4.54-101.3pgkg(-1) and 18.02-349.1pgkg(-1), respectively. Intra-day and inter-day RSDs were all lower than 3.6%. An obvious reduction in matrix effect was observed by this method compared with microwave assisted extraction followed by purification. The established method was sensitive, rapid, accurate and employable to simultaneously determine target analytes in farmed fish, river fish and marine fish.