Plasma Fluid Research Articles

Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Tofersen, an antisense oligonucleotide, has recently received FDA and EMA approval for treating amyotrophic lateral sclerosis (ALS) in adults with SOD1 gene mutations. This systematic review and meta-analysis synthesized evidence on tofersen's safety and efficacy in patients with SOD1-related ALS. A comprehensive search of three databases was conducted from inception through October 2024. Eligible studies included clinical trials, observational studies, and case studies. Meta-analyses were conducted using a random-effects model in RevMan. Twelve studies involving 195 patients treated with tofersen met the inclusion criteria, comprising two randomized controlled trials (RCTs), five cohort studies, one case series, and four case reports. Tofersen demonstrated promising effects, notably reducing SOD1 levels in cerebrospinal fluid and neurofilament light chain (NfL) in plasma, a biomarker strongly correlated with ALS progression and survival. Meta-analysis of RCTs showed a significantly lower rate of decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores from baseline in the tofersen group compared to placebo (SMD = 0.44, 95% CI [0.05 to 0.83], P = 0.03) and a significant reduction in the decline of predicted Slow Vital Capacity (P = 0.005). In a pre-post meta-analysis of five studies, a significant decrease in ALS progression rate (ALSFRS-R decline rate) was observed (MD = -0.28, 95% CI [-0.40 to -0.15], P < 0.0001). Reported adverse events were consistent with ALS progression or procedural effects. Current evidence suggests that tofersen effectively reduces SOD1 and NfL levels and slow disease progression in SOD1 ALS, showing promise as a targeted therapeutic option.

The development and application of an engineered direct electron transfer enzyme for continuous levodopa monitoring

Levodopa, the primary treatment for Parkinson’s Disease, has a narrow therapeutic window further complicated by the lack of real-time feedback, primarily due to the absence of an enzyme specific to levodopa. We addressed this by developing a novel direct electron transfer type (DET) enzyme, copper dehydrogenase (CoDH), engineered from an extremophile derived multicopper oxidase (MCO), for use in a continuous levodopa sensor. By introducing mutations into the type 2 and type 3 copper ligand histidine residues, the enzyme drastically decreased its oxidase activity while enhancing DET activity with the electrode. Using this developed CoDH, a chronoamperometric levodopa sensor was constructed, which was minimally affected by environmental changes, or by interferents, including levodopa metabolites, adjunct medications, and common plasma and interstitial fluid components. A miniaturized levodopa sensor was constructed and was able to detect levodopa as low as 138 nM, suggesting its future application for in vivo subcutaneous measurement.

The identification of plasma and cerebrospinal fluid metabolites causally associated with mental disorders from a genetic perspective.

Metabolomics research is a promising orientation for the diagnosis and intervention of several diseases, and observational studies have found many metabolic profiles to be associated with mental disorders. However, the causal relationship between plasma and cerebrospinal fluid (CSF) metabolites and mental disorders has not been established. We identified independent genetic variants associated with plasma, CSF metabolites, and mental disorders from pooled data in the published Genome-wide association studies (GWASs) and performed Mendelian randomization (MR) to investigate causal relationships. Genetic information on the screened mental disorders were derived from separate GWAS data sources as exploratory and validation datasets. Inverse variance weighting (IVW) was adopted as the primary method for MR analysis. We also applied sensitivity analyses to examine the reliability of the MR analysis results. Further enrichment analyses provided a deeper insight into the biological mechanisms of the three mental disorders. A dual analysis of the exploratory and validation datasets identified eight plasma metabolites and three CSF metabolites causally associated with MDD, two plasma metabolites and one CSF metabolite causally associated with anxiety disorders, and four plasma metabolites and two CSF causally associated with ASD. Horizontal pleiotropy and heterogeneity tests indicate the validity of our MR studies. Enrichment analysis uncovered metabolic pathways associated with disease. Our study identified plasma and cerebrospinal fluid metabolites that were causally associated with 3 mental disorders. Characterization of disease-associated metabolites not only deepens the understanding of pathological mechanisms, but also supports clinical diagnosis and prognosis.

Exosome Isolation from Pericardial Fluids.

Extracellular vehicles such as exosomes which lie in the size range of 30-150nm have gained significant attention due to their ability to contain molecular cargoes. These vesicles are released by various cells and are found to stably carry their molecular cargoes to recipient cells via different biological fluids. Therefore, exosomes isolated from various fluids such as plasma, urine, and pericardial fluid have been extensively studied in recent years. However, due to the miniscule nature of exosomes, isolation of exosomes from biological fluids has been a challenge, mainly due to low yields, contamination from large vesicles and proteins, and variable starting sample volumes. The following protocol describes the isolation of exosomes from human pericardial fluid samples collected from patients undergoing coronary artery bypass graft surgery. The exosomes isolated from these samples have been previously shown to have increased expression of cardiovascular molecular markers. Due to the precious nature of the patient samples, the exosomes isolated from this protocol have been validated to confirm their purity and viability for downstream applications.

Evaluation of the association between bevacizumab concentration and clinical outcomes in patients with breast cancer brain metastasis.

Bevacizumab is widely used in various clinical indications, but investigations into its optimal dosage for treating CNS metastases remain limited. The BEEP regimen, comprising bevacizumab, etoposide, and cisplatin, has recently demonstrated promising clinical outcomes for patients with breast cancer brain metastasis (BCBM) or leptomeningeal metastasis (LM). This study aimed to evaluate the exposure-response relationship of bevacizumab in BCBM patients and to explore the improved CNS penetration of chemotherapy by bevacizumab with LM patients. Twenty-two BCBM patients and six LM patients receiving the BEEP regimen were enrolled. For BCBM patients, blood samples were drawn at trough level of cycles 1 and 6 to investigate the association between bevacizumab concentrations and clinical outcomes. For LM patients, plasma and cerebrospinal fluid (CSF) concentrations of bevacizumab and etoposide were measured to investigate the enhancement of etoposide penetration provided by bevacizumab. Concentration evaluation revealed that bevacizumab plasma concentrations substantially varied between individuals. Additionally, concentrations increased after 6 cycles, indicating bevacizumab accumulation during treatment. Although bevacizumab concentrations did not associate with therapeutic response and progression-free survival, patients with higher bevacizumab concentrations exhibited longer overall survival (adjusted HR 0.78; p=0.039). Furthermore, a positive correlation was observed between time-weighted average concentration of plasma bevacizumab and CSF penetration of etoposide on day 2 (post-bevacizumab) relative to day 1 (pre-bevacizumab) (r=0.83; p=0.042). These findings offer valuable insights into the application of therapeutic drug monitoring of bevacizumab to improve survival outcomes in BCBM patients. Further studies are warranted to determine the optimal bevacizumab concentration.

Computational and numerical solutions to the Benney–Luke equation: Insights into nonlinear long wave dynamics in dispersive media

The current investigation seeks to explore the nonlinear Benney–Luke model, a governing equation pertinent to the propagation of extended waves within dispersive media, such as those observed in water waves and plasma waves, among other nonlinear wave phenomena. This model is distinguished by its incorporation of both dispersive and nonlinear effects, rendering it a valuable instrument for delving into intricate wave dynamics. Notably, it shares similarities with other prominent nonlinear evolution equations, including the Korteweg–de Vries (KdV) equation and the Boussinesq equation, both of which have been extensively examined within the domain of water waves and associated phenomena.Employing analytical methodologies, specifically the Khater (Khat III) and modified Kudryashov (MKud) methods, the research endeavors to derive exact solutions for the Benney–Luke equation. These solutions serve to elucidate various aspects of long wave behavior in dispersive media, encompassing their propagation characteristics, stability, and potential for inter-wave interactions. Furthermore, a trigonometric-quantic-B-spline (TQBS) scheme is adopted as a numerical approach to corroborate the precision of the derived analytical solutions and demonstrate their relevance across diverse physical scenarios linked to the model under examination.The research outcomes underscore the efficacy of the analytical techniques in generating dependable solutions for the Benney–Luke model. Moreover, through the utilization of the TQBS numerical scheme, the accuracy of the derived analytical solutions is affirmed, thereby ensuring their pragmatic utility across a spectrum of physical scenarios pertinent to the investigated model. This endeavor holds significance in its contribution towards advancing the comprehension of nonlinear wave phenomena within dispersive media, with ramifications spanning multiple disciplines, including fluid dynamics, plasma physics, and nonlinear optics. The novelty of this study lies in its application of the Khater (Khat III) and modified Kudryashov (MKud) methods to the Benney–Luke equation, alongside the integration of the TQBS numerical scheme for solution validation. Positioned within the domain of nonlinear partial differential equations, this research aligns with its broader applications in physics, particularly concerning the investigation of dispersive wave phenomena.

Zonal fields as catalysts and inhibitors of turbulence-driven magnetic islands

A novel coalescence process is shown to take place in plasma fluid simulations, leading to the formation of large-scale magnetic islands that become dynamically important in the system. The parametric dependence of the process on the plasma β and the background magnetic shear is studied, and the process is broken down at a fundamental level, allowing us to clearly identify its causes and dynamics. The formation of magnetic-island-like structures at the spatial scale of the unstable modes is observed quite early in the non-linear phase of the simulation for most cases studied, as the unstable modes change their structure from interchange-like to tearing-like. This is followed by a slow coalescence process that evolves these magnetic structures toward larger and larger scales, adding to the large-scale tearing-like modes that already form by direct coupling of neighboring unstable modes, but remain sub-dominant without the contribution from the smaller scales through coalescence. The presence of the cubic non-linearities retained in the model is essential in the dynamics of this process. The zonal fields are key actors of the overall process, acting as mediators between the competitive mechanisms from which turbulence-driven magnetic islands can develop. The zonal current is found to slow down the formation of large-scale magnetic islands, acting as an inhibitor, while the zonal flow is needed to allow the system to transfer energy to the larger scales, acting as a catalyst for the island formation process.

Follicular fluid and plasma lipidome profiling and associations towards embryonic development outcomes during ART treatment.

It is well acknowledged that lipids assume a critical role in oocyte maturation and early embryonic metabolism, this study aimed to evaluate the relationship between the lipid composition of plasma and follicular fluid (FF), and the consequences of embryonic development. This study compared the lipidomic profiles of paired plasma and FF samples obtained from sixty-five Chinese women who underwent assisted reproductive technology (ART) treatments. Non-targeted lipidomics analysis. Results not only indicated similarities in lipid composition between these biofluids, but also revealed a number of unique differences. The biomatrix distinction was found to be primarily driven by lipids belonging to the lysophosphatidylcholines (LPC), phosphatidylethanolamines (PE), ether PE, and triglyceride (TG) classes. In addition, specific species from these subclasses were discovered to be correlated with embryo development outcomes during ART. Notably, the composition of the fatty acyl chains appeared to play a crucial role in these associations. Furthermore, thirteen plasma lipid variables were identified, represented by Phosphatidylcholine 18:014:0 and PE P-18:020:1, which correlated with successful blastocyst formation (BF). The present study demonstrated that FF has a distinctive lipid composition, setting it apart from plasma; and the association observed with embryonic development underscored an important role of lipid composition in the healthy development of oocytes.

Penetration of linezolid into the pleural cavity in critically ill patients with proven or suspected Gram-positive bacterial infections: a retrospective pharmacokinetic study.

To describe the pharmacokinetics (PK) of linezolid in plasma and pleural fluid (PF) in critically ill patients with proven or suspected Gram-positive bacterial infections. Observational PK study in 14 critically ill patients treated with linezolid at standard doses. Blood and PF samples were collected and analysed by HPLC. The ratio between PF and plasma concentrations was calculated. The PK/pharmacodynamic (PD) target of linezolid in plasma was defined as 100% of the duration of the dosing interval in which concentrations were above the MIC (%100 T > MIC). The median (5th and 95th percentiles) linezolid concentration values for plasma pre-dose at steady state (Cmin,ss) and at the end of the 1-h infusion at steady state (Cmax,ss) were 1.1 (0.02-28.3) and 13.8 mg/L (2.9-38.1), respectively, and the PF pre-dose concentration (PF0 h) and PF concentration at the end of the 1-h intravenous infusion (PF1 h) were 2.8 (0.1-31.6) and 4.2 mg/L (0.1-45.2), respectively. At both times (pre-dose and post-infusion), a strong positive correlation was observed between PF and plasma linezolid concentrations (Spearman's rho coefficients = 0.8 and 0.9, with P < 0.001 for both). The defined PK/PD target in plasma was achieved in 8 (57.1%), 4 (28.6%) and 3 (21.4%) patients assuming an MIC of 1, 2 and 4 mg/L, respectively. Linezolid seems to penetrate well into the PF, with concentrations exceeding those in plasma. However, high inter-individual variability, both in plasma and PF concentrations, was observed. A high proportion of patients did not achieve the PK/PD target in plasma, especially in the presence of high MIC strains.

Identifying potential drug targets for myocardial infarction through Mendelian randomization

Background This study explored the associations between plasma and cerebrospinal fluid (CSF) proteins and myocardial infarction (MI) risk. Identifying specific proteins as biomarkers for MI could enhance our understanding of disease mechanisms and inform clinical practice. Methods We combined protein quantitative trait loci (pQTL) data for plasma and CSF proteins with genome-wide association study (GWAS) summary statistics for MI. Mendelian Randomization (MR) analyses were conducted to establish causal relationships, supported by Bayesian colocalization and Spearman correlation analyses. For plasma proteins, we used pQTL data from Cheng et al. to select 738 cis-acting SNPs associated with 734 proteins. The "TwoSampleMR" method and inverse-variance weighted MR were applied for evaluations. Results In plasma, CD8A and HDHD2 were identified as protective factors against MI, while DPEP1 was linked to increased risk. In CSF, CD30 Ligand was associated with MI risk. Bayesian colocalization supported the association for CD8A in plasma. No significant correlation was found between plasma and CSF results, suggesting distinct mechanisms for these biomarkers. Conclusion Our study identified several plasma and CSF proteins linked to MI risk, offering new insights into the disease’s biological underpinnings. These findings could guide future research on MI biomarkers and contribute to improved prevention and treatment strategies.

Diagnostic accuracy of phosphorylated tau217 in detecting Alzheimer's disease pathology among cognitively impaired and unimpaired: A systematic review and meta-analysis.

Our review summarizes the diagnostic accuracy of plasma and cerebrospinal fluid (CSF) phosphorylated tau 217 (p-tau217) in detecting amyloid and tau pathology on positron emission tomography (PET). We systematically reviewed studies that reported the diagnostic accuracy of plasma and CSF p-tau217, searching MEDLINE/PubMed, Scopus, and Web of Science through August 2024. The accuracy of p-tau217 in predicting amyloid and tau pathology on PET was evaluated in 30 studies. Both plasma and CSF p-tau217 effectively detect amyloid and tau PET deposition. Plasma p-tau217 showed 82% sensitivity for detecting amyloid and 83% for tau, with 86% and 83% specificity, respectively. CSF p-tau217 had 79% sensitivity for amyloid and 91% for tau, with 91% and 84% specificity. p-tau217 effectively identifies Alzheimer's disease (AD) pathology. Plasma p-tau217 was comparable to CSF p-tau217 in detecting amyloid deposition on PET. Despite being less sensitive for detecting tau deposition on PET, plasma p-tau217 can be an efficient screening tool for underlying AD pathology. HIGHLIGHTS: Plasma phosphorylated tau 217 (p-tau217) serves as a viable biomarker alternative to cerebrospinal fluid p-tau217 due to the strong concordance between their results. Plasma p-tau217 accurately identifies amyloid and tau positron emission tomography (PET) positivity, exhibiting a low rate of false negatives and positives, thereby establishing it as a reliable diagnostic tool for Alzheimer's disease (AD). Plasma p-tau217 demonstrates slightly higher accuracy in predicting amyloid PET positivity compared to tau PET positivity. Plasma p-tau217 demonstrates higher predictive accuracy in detecting AD pathology among cognitively impaired individuals, compared to cognitively unimpaired individuals, suggesting its enhanced utility as a diagnostic biomarker in clinical settings.

Nonplanar wave modulation and rogue wave formation in lunar dusty plasma

Abstract Motivated by the coming lunar missions, namely Luna-25 and Luna-27, scheduled for landing in the coming years, the investigation of the properties and characteristics of lunar dust, which, in contrast to terrestrial dust, adversely affects technology and creates significant risks to humans. As the Moon orbits Earth, plasma from its surroundings impacts its surface and dust grains above and below; thus, about one-third of the moon's orbit is occupied by the tail magnetosphere, which is thicker and more energetic than the tail regions' very thin plasma. Therefore, investigating the plasma properties in this region is of interest to avoid any unfavorable waves that may affect on the space vessels electronics. For this purpose, we use a three-component plasma fluid model study non-planar nonlinear electrostatic wave modulation on the lunar dark side. A non-planar, nonlinear Schrödinger equation (NLSE) is derived to examine the nonlinear wave envelope, which is produced from the dynamics of lunar negatively charged dust particles, positively charged ions, and Maxwellian electrons. Slow and fast dust-ion acoustic modes exist. The instability region allows the occurrence of nonlinear wave envelopes in the form of rogue waves. The latter are proposed as a physical, temporal, and spatial concentration of energy within a localized wave packet, which is sufficient to establish accumulation particles and influence the overall stability of the environment. The relative ion-to-electron temperature ratio enhances the fast mode's maximum growth rate. The growth rate of modulational instability for the spherical mode is lower than that for the cylindrical mode.

Temporal kinetics of serum amyloid A (SAA) concentration and identification of SAA isoforms in blood and synovial fluid of horses with experimentally induced septic arthritis, non-septic synovitis, and systemic inflammation.

Prompt diagnosis of equine septic arthritis is crucial for successful treatment. Serum amyloid A (SAA) has been suggested as a reliable biomarker. However, we previously found that synovial fluid SAA increases in nonaffected joints of horses with septic arthritis. We hypothesized that systemic SAA may leak into the nonaffected joints. If this is the case, we also hypothesized that locally produced joint SAA isoforms may be better candidates for septic arthritis biomarkers. Thus, our objectives were 1) to evaluate the temporal kinetics of systemic and synovial fluid SAA in horses with septic arthritis (n = 5), non-septic synovitis (n = 5), and systemic inflammation (n = 5), examining both affected and contralateral joints; and 2) investigate putative locally produced joint SAA isoforms and detect amino-acid differences between them. We confirmed that SAA increases significantly in synovial fluid in nonaffected joints of horses with systemic inflammation (≤352 mg/L), as well as in contralateral nonaffected joins in horses with septic arthritis (≤1,830 mg/L) compared to baseline at time 0 (<0.2 mg/L). We also identified a putative locally produced joint SAA peptide in synovial fluid (FGDSGHGAADSR) that differed in 1 amino acid from 2 systemic peptides found both in plasma and synovial fluid. The putative joint SAA isoform was present in joints of horses with both septic arthritis and systemic inflammation (ion intensities 104-106). Thus, the increase of synovial fluid SAA may be both due to the leakage of SAA from serum into joints and local production of joint SAA isoforms.

Increased Plasma β-Secretase 1 Activity Correlates With Neurodegeneration in Cerebral Small Vessel Disease.

β-secretase 1 (BACE1) plays a key role in amyloidogenic pathway and is considered a new mechanism for cerebral small vessel disease (CSVD). We explore the potential role of plasma BACE1 in CSVD and the pathological process it may be involved in. We enrolled 163 participants with CSVD (114 cerebral amyloid angiopathy and 49 hypertensive hemorrhage), and 96 cognitively unimpaired elders and 40 participants with Alzheimer'sdisease as controls. We measured BACE1 activity using a synthetic fluorescence substrate enzyme-linked immunosorbent assay. We used regression models to investigate associations between BACE1 and imaging and blood markers as well as clinical outcomes in CSVD. Plasma BACE1 activity was significantly higher in CSVD (median 862.0 relative fluorescence units [RFU], interquartile range 700.6-1032.9) compared with elder controls (522.5 RFU, 438.3-662.1, P<0.001) but lower than Alzheimer's disease (964.0 RFU, 838.4-1225.0, P=0.032). For CSVD, there was an association between plasma and cerebrospinal fluid BACE1 activity (β=0.50, P=0.030). Plasma BACE1 activity was negatively associated with hippocampal volume (coefficient -2.40, P<0.001), and positively associated with blood neurofilament light chain (coefficient 0.08, P<0.001) and total tau (coefficient 0.15, P=0.006) but not with specific cerebrovascular imaging markers. During 2-year follow-up, BACE1 activity was independently related to dementia conversion (odds ratio, 17.72; P=0.001) but not stroke in CSVD. Plasma BACE1 activity is moderately increased and associated with neurodegeneration and cognitive impairment risk in CSVD. It indicates that BACE1 is a promising biomarker especially for CSVD-related neurodegeneration.

204 Rumen-protected methionine modulates plasma and follicular fluid metabolites of beef cows

204 Rumen-protected methionine modulates plasma and follicular fluid metabolites of beef cows

Optical effects in unmagnetized cold plasmas by a chiral axion factor

Abstract Unmagnetized cold plasma modes are investigated in the context of the chiral Maxwell-Carroll-Field-Jackiw (MCFJ) electrodynamics, where the axion chiral factor acts retrieving some typical properties of magnetized plasmas. The Maxwell equations are rewritten for a cold, uniform, and collisionless fluid plasma model, allowing us to determine the dispersion relation, new refractive indices, and propagating modes. We find four distinct refractive indices modified by the purely timelike CFJ background that plays the magnetic conductivity chiral parameter role associated with right-circularly polarized (RCP) and left-circularly polarized (LCP) waves. For each refractive index, the propagation and absorption zones are determined and illustrated for some specific parameter values. Modified RCP and LCP helicons are found in the low-frequency regime. The optical behavior is investigated, revealing that the chiral factor induces birefringence, measured in terms of the rotatory power (RP). The dichroism coefficient is carried out for the absorbing zones. The negative refraction zones may enhance the involved RP, yielding RP sign reversion, a feature of rotating plasmas and MCFJ chiral plasmas. Charge density oscillations and Langmuir waves are also discussed, revealing no modified dispersion relation due to the chiral axion factor.

Alzheimer's Disease: In Vitro and In Vivo Evidence of Activation of the Plasma Bradykinin-Forming Cascade and Implications for Therapy.

The plaques associated with Alzheimer's disease are formed as a result of the aggregation of Aβ peptides, which vary in length from 38 to 43 amino acids. The 1-40 peptide is the most abundant, while the 1-42 peptide appears to be the most destructive to neurons and/or glial cells in a variety of assays. We have demonstrated that aggregated Aβ, a state prior to plaque formation, will activate the plasma bradykinin-forming pathway when tested in vitro. Aggregation is zinc-dependent, optimal at 25-50 µM, and the rate of aggregation is paralleled by the rate of activation of the bradykinin-forming pathway as assessed by plasma kallikrein formation. The aggregation of Aβ 1-38, 1-40, and 1-42 is optimal after incubation for 3 days, 3 h, and under 1 min, respectively. The cascade is initiated by the autoactivation of factor XII upon binding to aggregated Aβ; then, prekallikrein is converted to kallikrein, which cleaves high-molecular-weight kininogen (HK) to release bradykinin. Studies by a variety of other researchers have demonstrated the presence of each "activation-step" in either the plasma or spinal fluid of patients with Alzheimer's disease, including activated factor XII, kallikrein, and bradykinin itself. There is also evidence that activation is more prominent as dementia worsens. We now have medications that can block each step of the bradykinin-forming pathway as currently employed for the therapy of hereditary angioedema. Given the current state of therapy for Alzheimer's disease, which includes monoclonal antibodies that retard the rate of progression by 30% at most and have significant side effects, it seems imperative to explore prophylaxis using one of the long-acting agents that target plasma kallikrein or factor XIIa. There is a long-acting bradykinin antagonist in development, and techniques to target kallikrein mRNA to lower levels or knock out the prekallikrein gene are being developed.

Pharmacokinetics of pradofloxacin, florfenicol, and tulathromycin and response to treatment of steers experimentally infected with Mannheimia hemolytica.

Bovine respiratory disease (BRD) is an economically important disease in the beef industry, and a major driver of therapeutic antibiotic use. Pharmacokinetic data of these drugs is relatively limited in diseased animals. To determine the concentrations of pradofloxacin, florfenicol, and tulathromycin in the airways, plasma, and interstitial fluid (ISF) of steers with a clinically relevant model of bacterial respiratory disease. Twenty-four Holstein and Holstein/Jersey cross steers ranging in age from 6 to 15 months. A randomized, blinded clinical trial was performed. After transport stress, steers were inoculated with Mannheimia hemolytica to induce BRD. Upon onset of clinical disease, steers were treated with pradofloxacin, florfenicol or tulathromycin. Blood, ISF, and pulmonary epithelial lining fluid (PELF) samples were obtained for drug concentration determination. Clinical exams and thoracic ultrasound examinations were conducted daily. Animals were euthanized at the end of the study period to assess lung lesions. Pradofloxacin Cmax in PELF was 0.81 μg/mL (CV = 49.02%) and penetration into the PELF was 203.58% (72%). Florfenicol Cmax in PELF was 2.94 μg/mL (42.1%) and penetration was 230.08% (78.82%). Tulathromycin PELF Cmax was 0.9 μg/mL (45.03%) and PELF penetration was 518.97% (56.59%). There are differences in penetration of the drugs into the ISF and PELF compared to one another and previous data from healthy steers demonstrating the effect of disease on the PK of these drugs.

Comparative study of novel solitary wave solutions with unveiling bifurcation and chaotic structure modelled by stochastic dynamical system

Abstract In this study, we conduct a comprehensive investigation of the novel characteristics of the (2 + 1)-dimensional stochastic Hirota–Maccari System (SHMS), which is a prominent mathematical model with significant applications in the field of nonlinear science and applied mathematics. Specifically, SHMS plays a critical role in the study of soliton dynamics, nonlinear wave propagation, and stochastic effects in complex physical systems such as fluid dynamics, optics, and plasma physics. In order to account for the abrupt and significant fluctuation, the aforementioned system is investigated using a Wiener process with multiplicative noise in the Itô sense. The considered equation is studied by the new extended direct algebraic method (NEDAM) and the modified Sardar sub-equation (MSSE) method. By solving this equation, we systematically derived the novel soliton solutions in the form of dark, dark-bright, bright-dark, singular, periodic, exponential, and rational forms. Additionally, we also categorize and analyze the W-shape, M-shape, bell shape, exponential, and hyperbolic soliton wave solutions, which are not documented by researchers. The bifurcation, chaos and sensitivity analysis has been depicted which represent the applicability of the system in different dynamics. These findings greatly advance our knowledge of nonlinear wave events in higher-dimensional stochastic systems both theoretically and in terms of possible applications. These findings are poised to open new avenues for future research into the applicability of stochastic nonlinear models in various scientific and industrial domains.

Clinical application value of simultaneous plasma and bronchoalveolar lavage fluid metagenomic next generation sequencing in patients with pneumonia-derived sepsis

BackgroundDespite the increasing use of metagenomic next-generation sequencing (mNGS) in sepsis, identifying clinically relevant pathogens remains challenging. This study was aimed to evaluate the clinical utility of simultaneous plasma and bronchoalveolar lavage fluid (BALF) detection using mNGS.MethodsThis retrospective study enrolled 95 patients with pneumonia-derived sepsis (PDS) admitted to the intensive care unit (ICU) between October 2021 and January 2023. Patients were divided into two groups: mNGS group (n = 60) and the non-mNGS group (n = 35), based on whether simultaneous plasma and BALF mNGS were conducted. All patients underwent conventional microbiological tests (CMT), including bacterial/fungal culture of peripheral blood and BALF, as well as sputum culture, detection of 1, 3-beta-D- glucan in BALF and RT-PCR testing. The clinical data of the enrolled patients were collected, and the detection performance and prognosis of plasma mNGS, BALF mNGS and CMT were compared.ResultsThe mNGS group exhibited a lower mortality rate than the non-mNGS group (35.0% vs. 57.1%, P = 0.034). Simultaneous detection in dual-sample resulted in a higher proportion of microorganisms identified as definite causes of sepsis alert compared to detection in either plasma or BALF alone (55.6% vs. 20.8% vs. 18.8%, P<0.001). Acinetobacter baumannii, Stenotrophomonas maltophilia, Candida albicans, and human mastadenovirus B were the primary strains responsible for infections in PDS patients. Patients with lower white blood cells and neutrophil indices had a greater consistency in dual-sample mNGS. Patients in the mNGS group had more antibiotic adjustments compared to the non-mNGS group (85.71% vs. 33.33%, P<0.001). The percentage of neutrophils was a risk factor for mortality in PDS patients (P = 0.002).ConclusionDual sample mNGS has the advantage of detecting and determining the pathogenicity of more pathogens and has the potential to improve the prognosis of patients with PDS.