A method for the determination of eight benzenes (BTEXs) and twelve chlorobenzenes (CBs) in goat\'s milk by headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS/MS) was developed. The study investigated the impact of various factors such as extraction fiber type, salt amount, equilibrium conditions, and desorption conditions on the outcomes. Target analytes were separated on a DB-HeavyWAX column and quantified using the external standard method. The results showed that the target compounds had a good linear relationship in the range of 0.01 ∼ 50 μg/L (R2 > 0.997), the limit of detection (LOD) was 0.003 ∼ 0.150 μg/L, and the limit of quantification (LOQ) was 0.01 ∼ 0.50 μg/L. The average recoveries were 82%-116% and the relative standard deviation (RSD) was 0.8%-17.3% under the three addition levels of 1×, 2×, and 10 × LOQ. In a survey of twenty goat\'s milk samples, only ethylbenzene, xylenes, cumene, chlorobenzene, and 1,4-dichlorobenzene were detected at levels exceeding their respective limits of quantification. The method was evaluated using two ecological scales (Eco-Scale), GAPI and AGREEN, to verify its environmental friendliness and applicability. This method is simple, green, and efficient, which provides a certain theoretical basis for the production and quality safety evaluation of dairy products.

The design of a catalyst with multifunctional sites is one of the effective methods for low-temperature catalytic oxidation of chlorinated volatile organic compounds (CVOCs). The loss of redox sites and competitive adsorption of H2O prevalent in the treatment of industrial exhaust gases are the main reasons for the weak mineralization ability and poor water vapor resistance of V-based catalysts. In this work, platinum (Pt) is selected to combine with the V/CeO2 catalyst, which provides more redox sites and H2O dissociative activation sites and further enhances its catalytic performance. The results show that PtV/CeO2 achieves 90% of the CO2 yield at 318 °C and maintains excellent catalytic activity rather than continuous deactivation within 15 h after water vapor injection. The formation of Pt-O-V bonds enhances the redox ability and promotes deep oxidation of polychlorinated intermediates, accounting for the significantly improved mineralization ability of PtV/CeO2. The dissociative activation effect of Pt on H2O molecules strengthens the migration and activation of V-adsorbed H2O, precluding V-poisoning and notably improving water resistance. This study lays a solid foundation for the efficient degradation of chlorobenzene under humid conditions.

UNASSIGNED: Triple therapy (long-acting muscarinic antagonist/long-acting β2-agonist/inhaled corticosteroid) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence. This study assessed comparative adherence and persistence to single-inhaler triple therapy (SITT) versus MITT among patients with COPD in a real-world setting in Germany.
UNASSIGNED: This retrospective analysis using the WIG2 benchmark database identified patients with COPD newly initiating triple therapy with MITT or SITT (fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or formoterol/beclomethasone/glycopyrronium bromide [FOR/BDP/GLY]) November 2017-June 2019. Eligible patients were ≥35 years with 1 year\'s continual insurance prior to triple therapy initiation and no previous record of triple therapy. Inverse probability of treatment weighting was used to balance baseline characteristics. Adherence was measured using proportion of days covered (PDC) at 6, 12, and 18 months post-treatment initiation; persistence (time until treatment discontinuation) was measured at 6, 12, and 18 months, with a gap of >30 days used to define non-persistence.
UNASSIGNED: Of 5710 patients included in the analysis (mean age 66 years), 71.4% initiated MITT and 28.6% initiated SITT (FF/UMEC/VI: 41.4%; FOR/BDP/GLY: 58.6%). Mean PDC was higher among SITT versus MITT users at all time points; at each time point, mean PDC was highest among FF/UMEC/VI users. During the first 6 months following treatment initiation, higher adherence was exhibited by FF/UMEC/VI (29%) and FOR/BDP/GLY (19%) users versus MITT users. Over the entire observation period, FF/UMEC/VI users had the highest proportion of persistent patients; at 18 months, 16.5% of FF/UMEC/VI users were persistent versus 2.3% of MITT users.
UNASSIGNED: Patients initiating SITT in Germany had significantly higher adherence and persistence compared with patients initiating MITT over 6 to 18 months following treatment initiation. Among SITT, FF/UMEC/VI users had the highest proportion of adherence and persistence.

In this study, a novel strain Burkholderia stabilis TF-2 capable of assimilatory and co-metabolic degradation of chlorobenzenes was obtained. The interaction between chlorobenzene (CB) and target enzymes, as well as the metabolic pathways in TF-2, were elucidated using multi-omics and molecular docking techniques. Results of degradation experiments indicated that TF-2 assimilated CB at a rate of 0.22-0.66 mg·gcell-1·h-1 in concentrations of 20-200 mg L-1. Additionally, TF-2 also used sodium succinate and sodium citrate as substrates to co-metabolize CB, with degradation rates of 0.26-2.00 and 0.31-1.72 mol·gcell-1·h-1, respectively. Whole-genome sequencing revealed over 18 novel genes associated with aromatic hydrocarbon degradation in TF-2. Transcriptomic analysis showed that CB induced the high expression of 119 genes involved in CB metabolism and late mineralization. The significant up-regulation of the bedC1 (encoding a ring-hydroxylated dioxygenase), CatA (chlorocatechol 1,2-dioxygenase), pcaJ (3-oxoadipate CoA-transferase alpha subunit) and fadA (acetyl-CoA acyltransferase) genes facilitated CB metabolism. Based on these findings, a metabolic pathway for CB was constructed, with the key step involving ortho cleavage of the aromatic ring under the action of the catA gene. Furthermore, molecular docking revealed that CB bound to bedC1 with -4.5 kcal mol-1 through hydrophobic bonds, π-stacking, and a halogen bond. These results provide strong support for development of efficient strains to enhance the removal of chlorinated organic compounds.

BACKGROUND: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS.
METHODS: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA.
RESULTS: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV1, %MMEF, %PEF, and all IOS parameters.
CONCLUSIONS: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.

BACKGROUND: Previous studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control.
METHODS: From October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment.
RESULTS: A total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group.
CONCLUSIONS: In the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.

Molecular interaction fields (MIFs) are three-dimensional interaction maps that describe the intermolecular interactions expected to be formed around target molecules. In this paper, a method for the fast computation of MIFs using the approximation functions of quantum mechanics-level MIFs of small model molecules is proposed. MIF functions of N-methylacetamide with chlorobenzene, bromobenzene, and iodobenzene probes were precisely approximated and used to calculate the MIFs on protein surfaces. This method appropriately reproduced halogen-bond-formable areas around the ligand-binding sites of proteins, where halogen bond formation was suggested in a previous study.

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.
目的： 评估乌美溴铵/维兰特罗在真实世界临床实践中应用于中国患者的安全性。 方法： 采用前瞻性、多中心、单臂、观察性研究，在2020年12月14日至2022年1月30日，从中国的14家研究中心纳入在真实世界临床实践中接受乌美溴铵/维兰特罗治疗的患者，共随访24周。研究主要结局为随访期内不良事件和严重不良事件的发生率。 结果： 共纳入887例患者，年龄为（67.5±9.6）岁，其中男性689例（77.7%）。大多数患者（98.1%）有慢性阻塞性肺疾病史。468例患者（52.8%）报告了合并药物。在所有纳入的患者中，59例（6.7%）报告了不良事件，21例（2.4%）报告了严重不良事件，其中9例报告了致死性严重不良事件，10例报告了非致死性严重不良事件，2例同时报告了非致死性和致死性严重不良事件。所有严重不良事件，包括致死性事件，经研究者判定均与乌美溴铵/维兰特罗无关。6例（0.7%）发生药物不良反应，其严重程度均为轻度。3例（0.3%）患者报告的不良事件属于重要已确定或潜在风险，经研究者判定均与乌美溴铵/维兰特罗无关。 结论： 乌美溴铵/维兰特罗在真实世界临床实践中应用于中国患者具有良好的安全性，未观察到与该药相关的新的安全性信号。.

Microbial fuel cell (MFC) is a promising device for water decontamination and energy generation. However, the correlation between power generation and pollutant degradation has not been clarified. Herein, a ruthenium-activated carbon (Ru-AC) bioanode was constructed for chlorobenzenes (CBs) treatment. The pollutant tolerance was improved by Ru-AC anode, and the minimum removal efficiencies of CB and ortho-dichlorobenzene (o-DCB) reached 75.1 % and 69.3 %, respectively, which were considerably higher than those of other MFCs (16.3 %-39.7 %). Correspondingly, the maximum output voltage reached 360.7 mV for the Ru-AC anode, whereas the values obtained from others reached 45.2-149.6 mV. Interaction models were introduced to quantify the relationship between power generation and pollutant degradation. The conversion of highly toxic chlorophenols to organic acids could be accelerated by boosting the mass and electron transfer, thereby simultaneously enhancing CBs removal and power generation. This work provided important insights into pollutant-powered MFC development.

BACKGROUND: This cost-utility analysis assessed the long-term clinical and economic benefits of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy vs FF/VI or UMEC/VI from a Quebec societal perspective in patients with chronic obstructive pulmonary disease (COPD) with ≥1 moderate/severe exacerbation in the previous year.
METHODS: The validated GALAXY disease progression model was utilized, with parameters set to baseline and efficacy data from IMPACT. Treatment costs (2017 Canadian dollars [C$]) were estimated using Quebec-specific unit costs. Costs and health outcomes were discounted at 1.5 %/year. A willingness-to-pay threshold of C$50,000/quality-adjusted life year (QALY) was considered cost-effective. Outcomes modeled were exacerbation rates, QALYs, life years (LYs), costs and incremental cost-effectiveness ratios (ICERs). Subgroup analyses were performed according to prior treatment, exacerbation history in the previous year, and baseline lung function.
RESULTS: Over a lifetime horizon, FF/UMEC/VI resulted in more QALYs and LYs gained, at a small incremental cost compared with FF/VI and UMEC/VI. From a societal perspective, the estimated ICER for the base case was C$18,152/QALY vs FF/VI, and C$15,847/QALY vs UMEC/VI. For the subgroup analyses (FF/UMEC/VI compared with FF/VI and UMEC/VI), ICERs ranged from: C$17,412-25,664/QALY and C$16,493-18,663/QALY (prior treatment); C$15,247-19,924/QALY and C$15,444-28,859/QALY (exacerbation history); C$14,025-34,154/QALY and C$16,083-17,509/QALY (baseline lung function).
CONCLUSIONS: FF/UMEC/VI was predicted to improve outcomes and be cost-effective vs both comparators in the base case and all subgroup analyses, and based on this analysis would be an appropriate investment of health service funds in Quebec.
BACKGROUND: IMPACT trial NCT02164513.