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1.
Clin Nephrol ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606849

RESUMO

OBJECTIVE: We aimed to evaluate the effect of cyclophosphamide combined with glucocorticoid therapy on idiopathic membranous nephropathy through a multicenter open-label randomized controlled trial. MATERIALS AND METHODS: 92 patients with idiopathic membranous nephropathy admitted from March 2020 to September 2022 were included and assigned to a control group (n = 46) and a research group (n = 46) using a random number table. The control group was given glucocorticoid, and the research group was given cyclophosphamide combined with glucocorticoid. Clinical efficacy, renal function-related indicators (serum creatinine, blood urea nitrogen and albumin, and 24-hour urine protein quantification), inflammatory factors (interleukin (IL)-6, IL-18, transforming growth factor-ß, and tumor necrosis factor-α), immune function-related indicators (anti-phospholipase A2 receptor antibody, and T-lymphocyte subsets), oxidative stress-related indicators (heme oxygenase-1, superoxide dismutase, malondialdehyde, and nitric oxide), blood lipid-related indicators (total cholesterol, triacylglycerol, and low-density lipoprotein), and adverse reactions were compared. RESULTS: The overall remission rate of the research group was higher than that of the control group (93.48 vs. 78.26%, p < 0.05). After treatment, the research group had lower levels of 24-hour urine protein quantification, serum creatinine, blood urea nitrogen, IL-6, IL-18, transforming growth factor-ß, tumor necrosis factor-α, heme oxygenase-1, malondialdehyde, anti-phospholipase A2 receptor antibody, CD8+, total cholesterol, triacylglycerol and low-density lipoprotein, higher levels of albumin, superoxide dismutase, nitric oxide, and CD4+ and a higher CD4+/CD8+ ratio than the control group (p < 0.05). CONCLUSION: Cyclophosphamide combined with glucocorticoid therapy is effective for improving the overall remission rate and can suppress inflammatory responses and oxidative stress in patients with idiopathic membranous nephropathy.

2.
Circ Cardiovasc Interv ; : e013579, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629273

RESUMO

BACKGROUND: The prognostic impact of left atrial appendage (LAA) patency, including those with and without visible peri-device leak (PDL), post-LAA closure in patients with atrial fibrillation, remains elusive. METHODS: Patients with atrial fibrillation implanted with the WATCHMAN 2.5 device were prospectively enrolled. The device surveillance by cardiac computed tomography angiography was performed at 3 months post-procedure. Adverse events, including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular death, all-cause death, and the combined major adverse events (MAEs), were compared between patients with complete closure and LAA patency. RESULTS: Among 519 patients with cardiac computed tomography angiography surveillance at 3 months post-LAA closure, 271 (52.2%) showed complete closure, and LAA patency was detected in 248 (47.8%) patients, including 196 (37.8%) with visible PDL and 52 (10.0%) without visible PDL. During a median of 1193 (787-1543) days follow-up, the presence of LAA patency was associated with increased risks of stroke/TIA (adjusted hazard ratio for baseline differences, 3.22 [95% CI, 1.17-8.83]; P=0.023) and MAEs (adjusted hazard ratio, 1.12 [95% CI, 1.06-1.17]; P=0.003). Specifically, LAA patency with visible PDL was associated with increased risks of stroke/TIA (hazard ratio, 3.66 [95% CI, 1.29-10.42]; P=0.015) and MAEs (hazard ratio, 3.71 [95% CI, 1.71-8.07]; P=0.001), although LAA patency without visible PDL showed higher risks of MAEs (hazard ratio, 3.59 [95% CI, 1.28-10.09]; P=0.015). Incidences of stroke/TIA (2.8% versus 3.0% versus 6.7% versus 22.2%; P=0.010), cardiovascular death (0.9% versus 0% versus 1.7% versus 11.1%; P=0.005), and MAEs (4.6% versus 9.0% versus 11.7% versus 22.2%; P=0.017) increased with larger PDL (0, >0 to ≤3, >3 to ≤5, or >5 mm). Older age and discontinuing antiplatelet therapy at 6 months were independent predictors of stroke/TIA and MAEs in patients with LAA patency. CONCLUSIONS: LAA patency detected by cardiac computed tomography angiography at 3 months post-LAA closure is associated with unfavorable prognosis in patients with atrial fibrillation implanted with WATCHMAN 2.5 device. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03788941.

3.
Sci Total Environ ; 927: 172395, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608882

RESUMO

PVC microplastics (PVC-MPs) are environmental pollutants that interact with cadmium (Cd) to exert various biological effects. Ducks belong to the waterfowl family of birds and therefore are at a higher risk of exposure to PVC-MPs and Cd than other animals. However, the effects of co-exposure of ducks to Cd and PVC-MPs are poorly understood. Here, we used Muscovy ducks to establish an in vivo model to explore the effects of co-exposure to 1 mg/L PVC-MPs and 50 mg/kg Cd on duck pancreas. After 2 months of treatment with 50 mg/kg Cd, pancreas weight decreased by 21 %, and the content of amylase and lipase increased by 25 % and 233 %. However, exposure to PVC-MPs did not significantly affect the pancreas. Moreover, co-exposure to PVC-MPs and Cd worsened the reduction of pancreas weight and disruption of pancreas function compared to exposure to either substance alone. Furthermore, our research has revealed that exposure to PVC-MPs or Cd disrupted mitochondrial structure, reduced ATP levels by 10 % and 18 %, inhibited antioxidant enzyme activity, and increased malondialdehyde levels by 153.8 % and 232.5 %. It was found that exposure to either PVC-MPs or Cd can induce inflammation and fibrosis in the duck pancreas. Notably, co-exposure to PVC-MPs and Cd exacerbated inflammation and fibrosis, with the content of IL-1, IL-6, and TNF-α increasing by 169 %, 199 %, and 98 %, compared to Cd exposure alone. The study emphasizes the significance of comprehending the potential hazards linked to exposure to these substances. In conclusion, it presents promising preliminary evidence that PVC-MPs accumulate in duck pancreas, and increase the accumulation of Cd. Co-exposure to PVC-MPs and Cd disrupts the structure and function of mitochondria and promotes the development of pancreas inflammation and fibrosis.

4.
Sensors (Basel) ; 24(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38610348

RESUMO

This study introduces a neural network-based approach to predict dust emissions, specifically PM2.5 particles, during almond harvesting in California. Using a feedforward neural network (FNN), this research predicted PM2.5 emissions by analyzing key operational parameters of an advanced almond harvester. Preprocessing steps like outlier removal and normalization were employed to refine the dataset for training. The network's architecture was designed with two hidden layers and optimized using tanh activation and MSE loss functions through the Adam algorithm, striking a balance between model complexity and predictive accuracy. The model was trained on extensive field data from an almond pickup system, including variables like brush speed, angular velocity, and harvester forward speed. The results demonstrate a notable predictive accuracy of the FNN model, with a mean squared error (MSE) of 0.02 and a mean absolute error (MAE) of 0.01, indicating high precision in forecasting PM2.5 levels. By integrating machine learning with agricultural practices, this research provides a significant tool for environmental management in almond production, offering a method to reduce harmful emissions while maintaining operational efficiency. This model presents a solution for the almond industry and sets a precedent for applying predictive analytics in sustainable agriculture.

5.
J Chromatogr Sci ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576204

RESUMO

An analytical method was developed for the screening of 172 veterinary drugs in traditional Chinese medicine Galli Gigerii Endothelium Corneum by high-performance liquid chromatography tandem mass spectrometry. The samples were pretreated by a modified QuEChERS method. A Zorbax Eclipse plus C18 column (1.8 µm, 3.0 × 150 mm2, Agilent) was used for the separation of analytes by gradient elution. All analytes were detected by electrospray ionization mass spectrometry with multiple reaction monitoring mode. Good linearity with R ≥ 0.99 was exhibited for all analytes within the respective range. The recoveries of all monitored analytes ranged from 55.4 to 127.6% at three spiked levels (limit of quantitation-LOQ, 2-fold LOQ, 10-fold LOQ), with relative standard deviations <17.8%. The estimated LOQ levels were 0.2-20 µg/kg. The application of this method provides a reference for the safety control of traditional Chinese medicines.

6.
Sci Rep ; 14(1): 7648, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561388

RESUMO

Natural killer (NK) cells play essential roles in the tumor development, diagnosis, and prognosis of tumors. In this study, we aimed to establish a reliable signature based on marker genes in NK cells, thus providing a new perspective for assessing immunotherapy and the prognosis of patients with gastric cancer (GC). We analyzed a total of 1560 samples retrieved from the public database. We performed a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of gastric cancer and identified 377 marker genes for NK cells. By performing Cox regression analysis, we established a 12-gene NK cell-associated signature (NKCAS) for the Cancer Genome Atlas (TCGA) cohort, that assigned GC patients into a low-risk group (LRG) or a high-risk group (HRG). In the TCGA cohort, the areas under curve (AUC) value were 0.73, 0.81, and 0.80 at 1, 3, and 5 years. External validation of the predictive ability for the signature was then validated in the Gene Expression Omnibus (GEO) cohorts (GSE84437). The expression levels of signature genes were measured and validated in GC cell lines by real-time PCR. Moreover, NKCAS was identified as an independent prognostic factor by multivariate analysis. We combined this with a variety of clinicopathological characteristics (age, M stage, and tumor grade) to construct a nomogram to predict the survival outcomes of patients. Moreover, the LRG showed higher immune cell infiltration, especially CD8+ T cells and NK cells. The risk score was negatively associated with inflammatory activities. Importantly, analysis of the independent immunotherapy cohort showed that the LRG had a better prognosis and immunotherapy response when compared with the HRG. The identification of NK cell marker genes in this study suggests potential therapeutic targets. Additionally, the developed predictive signatures and nomograms may aid in the clinical management of GC.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Prognóstico , Sequência de Bases , Imunoterapia , RNA , Microambiente Tumoral
7.
Transl Pediatr ; 13(3): 499-507, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38590368

RESUMO

Background: Microphthalmia-associated transcription factor/transcription factor E (MiTF/TFE) translocation renal cell carcinoma (RCC) is a rare type of non-clear cell RCC (nccRCC), which is more common in females. Currently, there is no standardized treatment for advanced metastatic microphthalmia translocation RCC (MiT-RCC). The main treatment modalities include surgery, chemotherapy, immunotherapy, anti-vascular endothelial growth factor or vascular endothelial growth factor receptor (VEGFR) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and targeted therapy against the mesenchymal-epithelial transition (MET) factor signaling pathway. Case Description: We present the case of an 8-year-old male patient with hematuria and paroxysmal urinary pain. Based on tumor genetic testing results and targeted drug matching analysis, the patient underwent tumor biopsy, tumor radical surgery with vascular osteotomy, and cervicothoracic lymph node dissection. The patient was then treated with a combination of immunotherapy [sintilimab, a drug directed against programmed cell death receptor-1 (PD-1)] and VEGFR tyrosine kinase inhibitor (TKI) (from pazopanib to sunitinib). Throughout the 10 cycles of conventional chemotherapy (seven courses of sintilimab since the start of the third chemotherapy treatment), the patient's condition remained stable, with no tumor recurrence at the primary site. However, in the later stages, the patient developed a large amount of ascites, and the family requested discontinuation of treatment, ultimately leading to the patient's death. Conclusions: In this case report, we summarize the therapeutic strategy of a young patient with metastatic transcription factor E3 (TFE3) MiT-RCC. For this disease, early immunotherapy and the use of precision-targeted drugs may have a favorable impact on the survival prognosis of the patient but may still be of less benefit in children with advanced multiple metastases. Therefore, further research on tumor driver genes, among other treatment components, is urgently needed to improve precision therapy.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38593018

RESUMO

This article studies the trajectory planning problem of an autonomous vehicle for exploring a spatiotemporal field subject to a constraint on cumulative information. Since the resulting problem depends on the signal strength distribution of the field, which is unknown in practice, we advocate the use of a model-free reinforcement learning (RL) method to find the solution. Given the vehicle's dynamical model, a critical (and open) question is how to judiciously merge the model-based optimality conditions into the model-free RL framework for improved efficiency and generalization, for which this work provides some positive results. Specifically, we discretize the continuous action space by leveraging analytic optimality conditions for the minimum-time optimization problem via Pontryagin's minimum principle (PMP). This allows us to develop a novel discrete PMP-based RL trajectory planning algorithm, which learns a planning policy faster than those based on a continuous action space. Simulation results: 1) validate the effectiveness of the PMP-based RL algorithm and 2) demonstrate its advantages, in terms of both learning efficiency and the vehicle's exploration time, over two baseline methods for continuous control inputs.

10.
Medicine (Baltimore) ; 103(16): e37891, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640271

RESUMO

RATIONALE: Traumatic bronchial rupture in infants usually necessitates surgical intervention, with few reports documenting instances of multiple cardiac arrests occurring during surgery under conditions of severe hypoxemia. PATIENT CONCERNS: A 3-year-old boy after trauma presented with severe hypoxemia for 2 days and was urgently transferred to the operating room for surgery, 6 episodes of cardiac arrest happend during surgery. DIAGNOSES: The baby was diagnosed with bronchial rupture based on the history of trauma, clinica manifestations, and intraoperative findings. INTERVENTIONS: Intrathoracic cardiac compression and intravenous adrenaline were administrated. OUTCOMES: The normal sinus rhythm of the heart was successfully restored within 1 minute on each occasion, facilitating the smooth completion of the surgical procedure. By the end of surgery, SpO2 levels had rebounded to 95% and remained stable. LESSONS: Inadequate management of bronchial ruptures in infants frequently coincides with severe hypoxemia, necessitating immediate surgical intervention. Prompt identification and management of cardiac arrest by anesthetists during surgery is imperative to reduce mortality.


Assuntos
Epinefrina , Parada Cardíaca , Masculino , Lactente , Humanos , Pré-Escolar , Parada Cardíaca/etiologia , Ruptura/cirurgia , Ruptura/complicações , Hipóxia/complicações , Salas Cirúrgicas
11.
Org Lett ; 26(15): 3135-3139, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38563556

RESUMO

Herein, we present the first racemic total synthesis of the structurally complex monoterpene indole alkaloids rhynchines A-E, starting from commercially available methyl nicotinate and 3-(2-bromoethyl)-1H-indole. The success of our synthesis is attributed to the utilization of a bioinspired synthetic strategy, which facilitated the rapid construction of the pentacyclic core skeleton of the target molecules through biomimetic skeletal rearrangement and late-stage C-H oxidative cyclization. Additionally, silica-gel-promoted tautomerization played a crucial role as a strategic element in the chemical synthesis of rhynchines A and B.

12.
Medicine (Baltimore) ; 103(15): e37636, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38608065

RESUMO

This study aimed to investigate the clinical predictors, including traditional Chinese medicine tongue characteristics and other clinical parameters for chemotherapy-induced myelosuppression (CIM), and then to develop a clinical prediction model and construct a nomogram. A total of 103 patients with lung cancer were prospectively enrolled in this study. All of them were scheduled to receive first-line chemotherapy regimens. Participants were randomly assigned to either the training group (n = 52) or the test group (n = 51). Tongue characteristics and clinical parameters were collected before the start of chemotherapy, and then the incidence of myelosuppression was assessed after treatment. We used univariate logistic regression analysis to identify the risk predictors for assessing the incidence of CIM. Moreover, we developed a predictive model and a nomogram using multivariate logistic regression analysis. Finally, we evaluated the predictive performance of the model by examining the area under the curve value of the receiver operating characteristic, calibration curve, and decision curve analysis. As a result, a total of 3 independent predictors were found to be associated with the CIM in multivariate regression analysis: the fat tongue (OR = 3.67), Karnofsky performance status score (OR = 0.11), and the number of high-toxic drugs in chemotherapy regimens (OR = 4.78). Then a model was constructed using these 3 predictors and it exhibited a robust predictive performance with an area under the curve of 0.82 and the consistent calibration curves. Besides, the decision curve analysis results suggested that applying this predictive model can result in more net clinical benefit for patients. We established a traditional Chinese medicine prediction model based on the tongue characteristics and clinical parameters, which could serve as a useful tool for assessing the risk of CIM.


Assuntos
Antineoplásicos , Doenças da Medula Óssea , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Modelos Estatísticos , Prognóstico , Língua
13.
Phys Chem Chem Phys ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639921

RESUMO

In this study, we successfully synthesize palladium-decorated indium trioxide (Pd/In2O3) hybrid nanoclusters (NCs) using an advanced dual-target cluster beam deposition (CBD) method, a significant stride in developing high-performance ethanol sensors. The prepared Pd/In2O3 hybrid NCs exhibit exceptional sensitivity, stability, and selectivity to low concentrations of ethanol vapor, with a maximum response value of 101.2 at an optimal operating temperature of 260 °C for 6 at% Pd loading. The dynamic response of the Pd/In2O3-based sensor shows an increase in response with increasing ethanol vapor concentrations within the range of 50 to 1000 ppm. The limit of detection is as low as 24 ppb. The sensor exhibits a high sensitivity of 28.24 ppm-1/2, with response and recovery times of 2.7 and 4.4 seconds, respectively, for 100 ppm ethanol vapor. Additionally, the sensor demonstrates excellent repeatability and stability, with only a minor decrease in response observed over 30 days and notable selectivity for ethanol compared to other common volatile organic compounds. The study highlights the potential of Pd/In2O3 NCs as promising materials for ethanol gas sensors, leveraging the unique capabilities of CBD for controlled synthesis and the catalytic properties of Pd for enhanced gas-sensing performance.

14.
J Int Med Res ; 52(4): 3000605241245269, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38635897

RESUMO

Bronchopleural fistula (BPF) is a potentially fatal complication and remains a surgical challenge. Concomitant problems, such as pulmonary infection and respiratory failure, are typically the main contributors to mortality from BPF because of improper contact between the bronchial and pleural cavity. We present the case of a 75-year-old male patient with a history of right upper lobe lung cancer resection who developed complex BPFs. Following appropriate antibiotic therapy and chest tube drainage, we treated the fistulas using endobronchial valve EBV placement and local argon gas spray stimulation. Bronchoscopic treatment is the preferred method for patients who cannot tolerate a second surgery because it can help to maximize their quality of life. Our treatment method may be a useful reference for treating complex BPF.


Assuntos
Fístula Brônquica , Doenças Pleurais , Masculino , Humanos , Idoso , Qualidade de Vida , Broncoscopia/efeitos adversos , Fístula Brônquica/diagnóstico por imagem , Fístula Brônquica/etiologia , Fístula Brônquica/cirurgia , Doenças Pleurais/diagnóstico por imagem , Doenças Pleurais/etiologia , Doenças Pleurais/cirurgia , Antibacterianos/uso terapêutico
15.
Chemosphere ; 357: 142068, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636921

RESUMO

Due to limited land availability in municipal wastewater treatment plants, integrated fixed-film activated sludge (IFAS) technology offers significant advantages in improving nitrogen removal performance and treatment capacity. In this study, two systems, IFAS and Anaerobic-Anoxic-Oxic Activated sludge process (AAO), were compared by adjusting parameters such as hydraulic retention time (HRT), nitrifying solution recycle ratio, sludge recycle ratio, and dissolved oxygen (DO). The objective was to investigate pollutant removal capacity and differences in microbial community composition between the two systems. The study showed that, at an HRT of 12 h, the IFAS system exhibited an average increase of 5.76%, 8.85%, and 12.79% in COD, NH4+-N, and TN removal efficiency respectively, compared to the AAO system at an HRT of 16 h. The TP concentration in the IFAS system reached 0.82 mg/L without the use of additives. The IFAS system demonstrated superior effluent results under lower operating conditions of HRT, nitrification solution recycle ratio, and DO. The 16S rDNA analysis revealed higher abundance of denitrification-related associated flora, including Proteobacteria, Bacteroidetes, and Planctomycetota, in the IFAS system compared to the AAO system. Similarities were observed between microorganisms attached to the media and activated sludge in the anaerobic, anoxic, and oxic tanks. q-PCR analysis indicated that the incorporation of filler material in the IFAS system resulted in similar abundance of nitrifying bacteria genes on the biofilm as in the oxic tank. Additionally, denitrifying genes showed higher levels due to aeration scouring and the presence of alternating aerobic-anaerobic environments on the biofilm surface, enhancing nitrogen removal efficiency.

16.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1632-1640, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621948

RESUMO

This study aims to explore the effects of tetramethylpyrazine(TMP) on pharmacokinetics in plasma and brain dialysate and neuropathic pain in the rat model of partial sciatic nerve injury(SNI), and to investigate the correlation between the analgesic effect of TMP and its concentrations in the plasma and brain dialysate. Male SD rats were randomized into Sham, SNI, and SNI+TMP groups. Mechanical stimulation with von frey filaments and cold spray method were employed to evaluate the mechanical sensitivity and cold sensitivity of rats. Another two groups, Sham+TMP and SNI+TMP, were used to intubate the common jugular vein and implant microdialysis probes into the anterior cingulate gyrus(ACC), respectively.After intraperitoneal injection of TMP at a dose of 80 mg·kg~(-1), automatic blood collection and intracerebral microdialysis(perfusion rate of 1 µL·min~(-1)) systems were used to collect the blood and brain dialysate for 24 h. HSS T3 C_(18) reversed-phase chromatographic column(2.1 mm×50 mm, 2.5 µm) was used for liquid chromatographic separation. Gradient elution was carried out with the mobile phase of methanol-water(containing 0.005% formic acid) at a flow rate of 0.25 mL·min~(-1). Electrospray ion source was used for mass spectrometry, and the scanning mode was multi-reaction monitoring under the positive ion mode. The ion pairs for quantitative analysis were TMP m/z 137/122 and aspirin m/z 179/137, respectively. DAS 2.11 was used to calculate the pharmacokinetic parameters. The optimal time of TMP to exert the analgesia effect and inhibit cold pain sensitivity was 60 min after treatment. The TMP in the plasma and brain dialysate of SNI rats showed the T_(max) of 15 min and 30 min, the C_(max) of(2 866.43±135.39) and(1 462.14±197.38) µg·L~(-1), the AUC_(0-t) of(241 463.30±28 070.31) and(213 115.62±32 570.07) µg·min·L~(-1), the MRT_(0-t) of(353.13±47.73) and(172.16±12.72) min, and the CL_Z of 0.73 and 0.36 L·min·kg~(-1), respectively. The analgesic effect of TMP had a significant correlation with the blood drug concentration in the ACC, which indicated that this method was suitable for the detection of TMP in rat plasma and brain dialysate. The method is accurate, reliable, and sensitive and can realize the important value of the application of correlation analysis theory of "automatic blood collection-microdialysis/PK-PD" in the research on neuropathic pain.


Assuntos
Encéfalo , Neuralgia , Pirazinas , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Neuralgia/tratamento farmacológico , Nervo Isquiático , Analgésicos
17.
BMC Vet Res ; 20(1): 147, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643185

RESUMO

BACKGROUND: Gamithromycin is an effective therapy for bovine and swine respiratory diseases but not utilized for rabbits. Given its potent activity against respiratory pathogens, we sought to determine the pharmacokinetic profiles, antimicrobial activity and target pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with therapeutic effect of gamithromycin against Pasteurella multocida in rabbits. RESULTS: Gamithromycin showed favorable PK properties in rabbits, including high subcutaneous bioavailability (86.7 ± 10.7%) and low plasma protein binding (18.5-31.9%). PK analysis identified a mean plasma peak concentration (Cmax) of 1.64 ± 0.86 mg/L and terminal half-life (T1/2) of 31.5 ± 5.74 h after subcutaneous injection. For P. multocida, short post-antibiotic effects (PAE) (1.1-5.3 h) and post-antibiotic sub-inhibitory concentration effects (PA-SME) (6.6-9.1 h) were observed after exposure to gamithromycin at 1 to 4× minimal inhibitory concentration (MIC). Gamithromycin demonstrated concentration-dependent bactericidal activity and the PK/PD index area under the concentration-time curve over 24 h (AUC24h)/MIC correlated well with efficacy (R2 > 0.99). The plasma AUC24h/MIC ratios of gamithromycin associated with the bacteriostatic, bactericidal and bacterial eradication against P. multocida were 15.4, 24.9 and 27.8 h in rabbits, respectively. CONCLUSIONS: Subcutaneous administration of 6 mg/kg gamithromycin reached therapeutic concentrations in rabbit plasma against P. multocida. The PK/PD ratios determined herein in combination with ex vivo activity and favorable rabbit PK indicate that gamithromycin may be used for the treatment of rabbit pasteurellosis.


Assuntos
Doenças dos Bovinos , Lagomorpha , Infecções por Pasteurella , Pasteurella multocida , Doenças dos Suínos , Coelhos , Animais , Bovinos , Suínos , Antibacterianos/uso terapêutico , Antibacterianos/farmacocinética , Infecções por Pasteurella/tratamento farmacológico , Infecções por Pasteurella/veterinária , Infecções por Pasteurella/microbiologia , Macrolídeos/uso terapêutico , Macrolídeos/farmacocinética , Testes de Sensibilidade Microbiana/veterinária , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Suínos/tratamento farmacológico
18.
Infect Dis Model ; 9(2): 618-633, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38645696

RESUMO

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010-2019. The burdens of five categories of disease causes - cardiovascular diseases, infectious respiratory diseases, injuries, metabolic diseases, and non-infectious respiratory diseases - were designated as intermediate outcome variables. The cumulative burden of these five categories, referred to as the total HTD burden, was the final outcome variable. We evaluated the predictive performance of eight models and subsequently introduced twelve intervention measures, allowing us to explore optimal decision-making strategies and assess their corresponding contributions. Our model selection results demonstrated the superior performance of the Graph Neural Network (GNN) model across various metrics. Utilizing simulations driven by the GNN model, we identified a set of optimal intervention strategies for reducing disease burden, specifically tailored to the seven major regions: East Asia and Pacific, Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. Sectoral mitigation and adaptation measures, acting upon our categories of Infrastructure & Community, Ecosystem Resilience, and Health System Capacity, exhibited particularly strong performance for various regions and diseases. Seven out of twelve interventions were included in the optimal intervention package for each region, including raising low-carbon energy use, increasing energy intensity, improving livestock feed, expanding basic health care delivery coverage, enhancing health financing, addressing air pollution, and improving road infrastructure. The outcome of this study is a global decision-making tool, offering a systematic methodology for policymakers to develop targeted intervention strategies to address the increasingly severe challenge of HTDs in the context of global warming.

19.
Food Chem ; 449: 139222, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38583398

RESUMO

Nine varieties of purple sweet potato were steamed and used for the production of shrimp freshness indicators. The impact of purple sweet potato's variety on the structure, physical property and halochromic ability of indicators was determined. Results showed different varieties of purple sweet potato had different starch, crude fiber, pectin, protein, fat and total anthocyanin contents. The microstructure, crystallinity, moisture content, water vapor permeability, tensile strength and elongation at break of indicators were affected by crude fiber content in purple sweet potato. The color, transmission and halochromic ability of indicators was associated with the total anthocyanin content in purple sweet potato. Freshness indicators produced from Fuzi No. 1, Ganzi No. 6, Ningzi No. 2, Ningzi No. 4, Qining No. 2 and Qining No. 18 of purple sweet potato were suitable to indicate shrimp freshness. This study provides useful information on screening suitable varieties of purple sweet potato for intelligent packaging.

20.
Food Sci Nutr ; 12(3): 1888-1901, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38455194

RESUMO

The present study used gas chromatography-mass spectrometry (GC-MS) and gas chromatography-ion mobility spectrometry (GC-IMS) to separate and identify the characteristic volatile flavor substances in 30 roasted peanut samples. GC-MS identified 59 volatile compounds, and GC-IMS detected 61 volatile flavor substances. The 30 peanut varieties were then divided into four groups on the basis of their volatile flavor substances using principal component analysis (PCA), and a fingerprint profile of the varieties' volatile characteristics was established from information peaks identified in the spectra. Descriptive sensory analysis (DSA) was performed to distinguish differences in flavor attributes between roasted peanut varieties. Partial least squares regression (PLSR) was performed with the volatile flavor content of roasted peanuts as the independent variable and the flavor attribute score as the dependent variable. These findings provide a basis for predicting the appeal of roasted peanuts based on their composition and demonstrate a potential avenue for improving food flavor quality.

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