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This study aimed to determine whether caffeine gum influenced perceptual-cognitive and physical performance during the extra-time period of simulated soccer match-play. Semiprofessional male soccer players (n = 12, age: 22 ± 3 years, stature: 1.78 ± 0.06 m, mass: 75 ± 9 kg) performed 120-min soccer-specific exercise on two occasions. In a triple-blind, randomized, crossover design, players chewed caffeinated (200 mg; caffeine) or control (0 mg; placebo) gum for 5 min following 90 min of soccer-specific exercise. Perceptual-cognitive skills (i.e., passing accuracy, reaction time, composure, and adaptability) were assessed using a soccer-specific virtual reality simulator, collected pre- and posttrial. Neuromuscular performance (reactive-strength index, vertical jump height, absolute and relative peak power output, and negative vertical displacement) and sprint performance (15 and 30 m) were measured at pretrial, half-time, 90 min, and posttrial. Caffeine gum attenuated declines in reaction time (pre: 90.8 ± 0.8 AU to post: 90.7 ± 0.8 AU) by a further 4.2% than placebo (pre: 92.1 ± 0.8 AU to post: 88.2 ± 0.8 AU; p <.01). Caffeine gum reduced composure by 4.7% (pre: 69.1 ± 0.8 AU to post: 65.9 ± 0.8 AU) versus placebo (pre: 68.8 ± 0.8 AU to post: 68.3 ± 0.8 AU; p <.01). Caffeine gum did not influence any other variables (p >.05). Where caffeine gum is consumed by players prior to extra-time, reaction time increases but composure may be compromised, and neuromuscular and sprint performance remain unchanged. Future work should assess caffeine gum mixes with substances like L-theanine that promote a relaxed state under stressful conditions. [ABSTRACT FROM AUTHOR]

Purpose: Total hemoglobin mass (tHbmass) and blood volume (BV) are important determinants of maximal oxygen uptake and endurance capacity. Higher-caliber endurance athletes usually possess higher tHbmass and BV values. This study aimed to compare tHbmass and BV among swimmers of diverse competitive calibers and distances. Methods: Thirty swimmers (16 female and 14 male) participated in the study: 3 were tier 5, world class (869 [59] FINA points); 15 were tier 4, elite/international (853 [38] points); and 12 were tier 3, highly trained/national (808 [35] points). They specialized in competition distances ranging from 200 m to open-water 10 km. Between February 2019 and February 2020, all swimmers had their tHbmass and BV measured by carbon monoxide rebreathing 1 to 6 times and participated in multiple competitions and race events. Results: Relative tHbmass and BV were not different (P >.05) between tiers among women or among men (pooled tHbmass values 14.5 [0.5], 12.5 [1.5], 12.6 [2.3] g/kg for tier 5, tier 4, and tier 3, respectively). No differences were observed in relative tHbmass (P =.215) and BV (P =.458) between pool and open-water swimmers or between 200-, 400-, and 1500-m specialists (P >.05). No significant correlations were found between the highest measured absolute or relative tHbmass and BV and the highest FINA points scored over the follow-up period (R = −.42–.17, P =.256–.833), irrespective of competition distance. Conclusion: tHbmass and BV values did not differ between swimmers of different calibers or among competition distances. Furthermore, these values did not correlate with FINA points, either in males or in females. The present results indicate that hematological characteristics may have a lesser impact on swimming performance than on land-based endurance sports. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic fluorine-containing compounds largely used in industrial and consumer applications. They tend to bioaccumulate in the human body after intake from various sources in daily life. Following repeated exposure to PFAS, a broad range of adverse health outcomes has been reported. Consequently, monitoring PFAS levels in human blood is of paramount importance for public health policies. In contrast with traditional venipuncture, dried blood spots (DBS) constitute a reliable, cheap, and less invasive technique to allow microsampling by capillary blood collected on a specific device. This work aimed to develop and validate an innovative analytical method, combining quantitative DBS with UHPLC-MS/MS instrumentation to identify and quantify 25 PFAS. The extraction procedure was developed and optimized within the range 2–100 ng/mL. Specifically, fortified blood was applied on Capitainer®B devices providing 10 μL of blood volume through a microfluidic channel. After 3 h of drying, the extraction was performed by methanol under sonication, followed by centrifugation. Then, the extraction solvent was evaporated; the residue was reconstituted with the mobile phase solution. The validated method evidenced good sensitivity, with limits of detection ranging from 0.4 ng/mL (PFODA, PFOS) to 1.0 ng/mL (PFOA, 3,6-OPFHpA). The ± 20% acceptability criteria established for intra- and inter-day precision and accuracy were fulfilled for all analytes. High recovery—above 80%—was recorded, whereas significant matrix effect resulted in ion enhancement (> 50%) for 13 analytes. In conclusion, the proposed workflow proved to be reliable, fit for purpose, and easily adaptable in the laboratory routine. [ABSTRACT FROM AUTHOR]

Background: This Intensive Care Medicine Rapid Practice Guideline (ICM‐RPG) provides an evidence‐based recommendation to address the question: in adult patients in intensive care units (ICUs), should we use small‐volume or conventional blood collection tubes? Methods: We included 23 panelists in 8 countries and assessed and managed financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. We conducted a systematic review, including evidence from observational and randomized studies. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, we evaluated the certainty of evidence and developed recommendations using the Evidence‐to‐Decision framework. Results: We identified 8 studies (1 cluster and 2 patient‐level randomized trials; 5 observational studies) comparing small‐volume to conventional tubes. We had high certainty evidence that small‐volume tubes reduce daily and cumulative blood sampling volume; and moderate certainty evidence that they reduce the risk of transfusion and mean number of red blood cell units transfused, but these estimates were limited by imprecision. We had high certainty that small‐volume tubes have a similar rate of specimens with insufficient quantity. The panel considered that the desirable effects of small‐volume tubes outweigh the undesirable effects, are less wasteful of resources, and are feasible, as demonstrated by successful implementation across multiple countries, although there are upfront implementation costs to validate small‐volume tubes on laboratory instrumentation. Conclusion: This ICM‐RPG panel made a strong recommendation for the use of small‐volume sample collection tubes in adult ICUs based on overall moderate certainty evidence. [ABSTRACT FROM AUTHOR]

Background: Hemodynamic monitoring is crucial for the comprehensive management of children with sepsis, particularly those involving the kidneys. Sepsis-associated acute kidney injury (S-AKI) is closely linked to poor outcomes. Recently, ultrasonography modalities have been widely accepted as a non-invasive, rapid, and reliable tool for assessing volume status. We conducted research to determine intravascular volume based on ultrasound examination in S-AKI patients. Methods: A prospective cohort study was conducted between December 2023 and March 2024 in the Pediatric Intensive Care Unit (PICU) at Hasan Sadikin General Hospital. We divided the patients into two groups: those with sepsis without AKI and those with S-AKI. The intravascular volume was measured by the IVC/Ao (inferior vena cava/abdominal aorta) ratio using two-dimensional ultrasonography and USCOM before and 24 h after fluid treatment. The results were analyzed using SPSS 25, with a significance level of p < 0.05. Results: A total of 36 pediatric patients (aged 1 month–18 years) with sepsis were included. The IVC/Ao ratio before and after the fluid intervention demonstrated significant differences between the two groups (p < 0.001). USCOM Cardiac Index (CI) before and after the intervention also showed significant differences between the two groups (p < 0.001). Patients with S-AKI exhibited a poor hemodynamic response in the IVC/Ao ratio two-dimensional ultrasonography and USCOM examination. Conclusions: IVC/Ao ratio measurement is as accurate as USCOM and can be used as a simple and cost-effective alternative for hemodynamic monitoring. [ABSTRACT FROM AUTHOR]

ITER is of key importance in the European fusion roadmap as it aims to prove the scientific and technological feasibility of fusion as a future energy source. The EUROfusion consortium of labs within Europe is contributing to the preparation of ITER scientific exploitation and operation and aspires to exploit ITER outcomes in view of DEMO. The paper provides an overview of the major progress obtained recently, carried out in the frame of the new (initiated in 2021) EUROfusion work-package called ' Pr eparation of I TER O peration' (PrIO). The overview paper is directly supported by the eleven EUROfusion PrIO contributions given at the 29th Fusion Energy Conference (16–21 October 2023) London, UK [www.iaea.org/events/fec2023]. The paper covers the following topics: (i) development and validation of tools in support to ITER operation (plasma breakdown/burn-through with evolving plasma volume, new infra-red synthetic diagnostic for off-line analysis and wall monitoring using Artificial Intelligence techniques, synthetic diagnostics development, development and exploitation of multi-machine databases); (ii) R&D for the radio-frequency ITER neutral beam sources leading to long duration of negative deuterium/hydrogen ions current extraction at ELISE and participation in the neutral beam test facility with progress on the ITER source SPIDER, and, the commissioning of the 1 MV high voltage accelerator (MITICA) with lessons learned for ITER; (iii) validation of neutronic tools for ITER nuclear operation following the second JET deuterium–tritium experimental campaigns carried out in 2021 and in 2023 (neutron streaming and shutdown dose rate calculation, water activation and activated corrosion products with advanced fluid dynamic simulation; irradiation of several materials under 14.1 MeV neutron flux etc). [ABSTRACT FROM AUTHOR]

Context Renin is a marker of blood volume. There is no consensus on the validity of plasma renin measurement for adjusting mineralocorticoid (MC) substitution in patients with primary adrenal insufficiency (PAI). Objective This work aimed to investigate if plasma renin could be used to adjust MC substitution in patients with PAI. Methods A total of 150 patients with at least one measurement of plasma renin followed for PAI at 2 tertiary expert centers between 2008 and 2022 were retrospectively included. As supraphysiological hydrocortisone might have additional MC activity, we integrated the individual hydrocortisone dose to obtain the MC equivalent dose (Eq-MC). Renin less than 20 mIU/L was considered oversubstituted, renin between 20 and 60 mIU/L as correctly substituted, and renin over 60 mIU/L as undersubstituted. Results The mean dose of fludrocortisone was 82.3 ± 46 μg/day. Plasma renin was abnormal in 56.7% of cases (7 patients oversubstituted and 78 patients undersubstituted). Abnormalities in electrolyte levels were observed in only 12.7% of patients. Plasma renin correlated negatively with sodium (P <.01) and systolic blood pressure (P =.026), and positively with potassium (P <.01). Doses changes in Eq-MC had a statistically significant effect on renin levels (P =.0037), with an increase of MC dose correlating with a decrease in renin level and vice versa; no correlation was observed using electrolytes or blood pressure. Conclusion Plasma renin correlates with electrolytes and blood pressure. While dose changes significantly alter renin levels, electrolytes and blood pressure do not, suggesting that renin may provide more information about MC replacement therapy than electrolytes and blood pressure. [ABSTRACT FROM AUTHOR]

BACKGROUND Inhibitors of the Na+-coupled glucose transporter SGLT2 (SGLT2i) primarily shift the reabsorption of large amounts of glucose from the kidney's early proximal tubule to downstream tubular segments expressing SGLT1, and the non-reabsorbed glucose is spilled into the urine together with some osmotic diuresis. How can this protect the kidneys and heart from failing as observed in individuals with and without type 2 diabetes? GOAL Mediation analyses identified clinical phenotypes of SGLT2i associated with improved kidney and heart outcome, including a reduction of plasma volume or increase in hematocrit, and lowering of serum urate levels and albuminuria. This review outlines how primary effects of SGLT2i on the early proximal tubule can explain these phenotypes. RESULTS The physiology of tubule-glomerular communication provides the basis for acute lowering of GFR and glomerular capillary pressure, which contributes to lowering of albuminuria but also to long term preservation of GFR, at least in part by reducing kidney cortex oxygen demand. Functional co-regulation of SGLT2 with other sodium and metabolite transporters in the early proximal tubule explains why SGLT2i initially excrete more sodium than expected and are uricosuric, thereby reducing plasma volume and serum urate. Inhibition of SGLT2 reduces early proximal tubule gluco-toxicity and by shifting transport downstream may simulate "systemic hypoxia", and the resulting increase in erythropoiesis, together with the osmotic diuresis, enhances hematocrit and improves blood oxygen delivery. Cardio-renal protection by SGLT2i is also provided by a fasting-like and insulin-sparing metabolic phenotype and, potentially, by off-target effects on the heart and microbiotic formation of uremic toxins. [ABSTRACT FROM AUTHOR]

The presence of a normal large blood vessel (LBV) in a tumor region can impact the evaluation of quantitative dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) parameters and tumor classification. Hence, there is a need for automatic removal of LBVs from brain tissues including intratumoral regions for achieving an objective assessment of tumors. This retrospective study included 103 histopathologically confirmed brain tumor patients who underwent MRI, including DCE‐MRI data acquisition. Quantitative DCE‐MRI analysis was performed for computing various parameters such as wash‐out slope (Slope‐2), relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), blood plasma volume fraction (Vp), and volume transfer constant (Ktrans). An approach based on data‐clustering algorithm, morphological operations, and quantitative DCE‐MRI maps was proposed for the segmentation of normal LBVs in brain tissues, including the tumor region. Here, three widely used data‐clustering algorithms were evaluated on two types of quantitative maps: (a) Slope‐2, and (b) a new proposed combination of rCBV and Slope‐2 maps. Fluid‐attenuated inversion recovery‐MRI hyperintense lesions were also automatically segmented using deep learning‐based architecture. The accuracy of LBV segmentation was qualitatively assessed blindly by two experienced observers, and Likert scoring was also obtained from each individual and compared using Cohen's Kappa test, and multiple statistical features from quantitative DCE‐MRI parameters were obtained in the segmented tumor. t‐test and receiver operating characteristic (ROC) curve analysis were performed for comparing the effect of removal of LBVs on parameters as well as on tumor grading. k‐means clustering exhibited better accuracy and computational efficiency. Tumors, in particular high‐grade gliomas (HGGs), showed a high contrast compared with normal tissues (relative % difference = 18.5%) on quantitative maps after the removal of LBVs. Statistical features (95th percentile values) of all parameters in the tumor region showed a statistically significant difference (p < 0.05) between with and without LBV maps. Similar results were obtained for the ROC curve analysis for differentiation between low‐grade gliomas and HGGs. Moreover, after the removal of LBVs, the rCBV, rCBF, and Vp maps show better visualization of tumor regions. [ABSTRACT FROM AUTHOR]

Clinical congestion remains a major cause of hospitalization and re-hospitalizations in patients with chronic heart failure (HF). Despite the high prevalence of this issue and clinical concern in HF practice, there is limited understanding of the complex pathophysiology relating to the "congestion" of congestive HF. There is no unifying definition or clear consensus on what is meant or implied by the term "congestion." Further, the discordance in study findings relating congestion to physical signs and symptoms of HF, cardiac hemodynamics, or metrics of weight change or fluid loss with diuretic therapy has not added clarity. In this review, these factors will be discussed to add perspective to this issue and consider the factors driving "congestion." There remains a need to better understand the roles of fluid retention promoting intravascular and interstitial compartment expansions, blood volume redistribution from venous reservoirs, altered venous structure and capacity, elevated cardiac filling pressure hemodynamics, and heterogeneous intravascular volume profiles (plasma volume and red blood cell mass) with a goal to help demystify "congestion" in HF. Further, this includes highlighting the importance of recognizing that congestion is not the result of a single pathway but a complex of responses some of which produce symptoms while others do not; yet, we confine these varied responses to the single and somewhat vague term "congestion." [ABSTRACT FROM AUTHOR]

Purpose: Multiparametric arterial spin labeling (MP‐ASL) can quantify cerebral blood flow (CBF) and arterial cerebral blood volume (CBVa). However, its accuracy is compromised owing to its intrinsically low SNR, necessitating complex and time‐consuming parameter estimation. Deep neural networks (DNNs) offer a solution to these limitations. Therefore, we aimed to develop simulation‐based DNNs for MP‐ASL and compared the performance of a supervised DNN (DNNSup), physics‐informed unsupervised DNN (DNNUns), and the conventional lookup table method (LUT) using simulation and in vivo data. Methods: MP‐ASL was performed twice during resting state and once during the breath‐holding task. First, the accuracy and noise immunity were evaluated in the first resting state. Second, CBF and CBVa values were statistically compared between the first resting state and the breath‐holding task using the Wilcoxon signed‐rank test and Cliff's delta. Finally, reproducibility of the two resting states was assessed. Results: Simulation and first resting‐state analyses demonstrated that DNNSup had higher accuracy, noise immunity, and a six‐fold faster computation time than LUT. Furthermore, all methods detected task‐induced CBF and CBVa elevations, with the effect size being larger with the DNNSup (CBF, p = 0.055, Δ = 0.286; CBVa, p = 0.008, Δ = 0.964) and DNNUns (CBF, p = 0.039, Δ = 0.286; CBVa, p = 0.008, Δ = 1.000) than that with LUT (CBF, p = 0.109, Δ = 0.214; CBVa, p = 0.008, Δ = 0.929). Moreover, all the methods exhibited comparable and satisfactory reproducibility. Conclusion: DNNSup outperforms DNNUns and LUT with respect to estimation performance and computation time. [ABSTRACT FROM AUTHOR]

Background: The significance of computed tomography (CT)-based volume measurement of the inferior vena cava (IVC) in the treatment and prognosis of trauma patients is not yet fully understood. The conflicting results that have been reported may be attributable to differences in injury severity and the use of different measurement methods, including IVC index and volumetry. The purpose of this study was to determine the relationship between IVC volume and red blood cell (RBC) transfusion and mortality in intubated trauma patients who were stable enough for initial CT imaging. Methods: A retrospective analysis was conducted on all consecutive trauma patients who underwent emergency tracheal intubation and mechanical ventilation before initial whole-body CT imaging at a level-1 trauma center over a 12-year period (2008–2019). The IVC volume was determined on initial trauma CT and included in multivariable models with demographic and diagnostic data. Associations of overall RBC transfusion, massive transfusion, 24-h mortality, and 30-day mortality were assessed using logistic regression analyses and Cox proportional hazard models. Results: A total of 438 patients (75.3% male) with a median age of 50 years, and a median injury severity score (ISS) of 26 points were included in the analysis. Most of the patients (97.5%) had suffered from blunt trauma mechanisms. Median IVC volume was 36.25 cm3, and RBC transfusion and massive transfusion were performed in 197 and 90 patients, respectively. The 24-h and 30-day mortality rates were 7.3% and 23.3%, respectively. VCI volume was found to be independently associated with the necessity of RBC transfusion and 24-h mortality (OR 0.98, 95% CI 0.96–0.99, p = 0.01 and HR 0.96, 95% CI 0.93–0.99, p = 0.025, respectively), while associations with massive transfusion and 30-day mortality were not statistically significant in multivariable analyses. Conclusion: Initial IVC volume may serve as a predictor of patients at risk for overall RBC transfusion requirements and 24-h mortality, suggesting the possibility of its diagnostic efficacy in short-term outcomes. Further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Positive end-expiratory pressure results in a sustained positive intrathoracic pressure, which exerts pressure on intrathoracic vessels, resulting in cardiopulmonary interactions. This sustained positive intrathoracic pressure is known to decrease cardiac preload, and thus, decrease venous return, ultimately reducing both the stroke volume and stressed blood volume of the cardiovascular system. Currently, cardiovascular and pulmonary care are provided independently of one another. That positive end-expiratory pressure alters both stroke volume and stressed blood volume suggests both the pulmonary and cardiovascular state should be conjointly optimised. Optimising these systems in isolation may benefit one system, but have highly detrimental effects on the other. A combined cardiopulmonary model has the potential to provide a better understanding of patient specific pulmonary and cardiovascular state, as well as resulting cardiopulmonary interactions. This would enable simultaneous optimisation of all cardiovascular and pulmonary parameters. Cardiopulmonary interactions are highly patient specific and unpredictable, making accurate modelling of these interactions challenging. A previously validated cardiopulmonary model was found to have increasing errors at high positive end-expiratory pressures. A new iteration, the alpha model, was introduced to resolve this issue. This paper aims to review the alpha model against its predecessors, the previous cardiopulmonary model, and the original three chamber cardiovascular system model. All models are used to identify cardiovascular system parameters from measurements of 4 pigs during a preload reduction manoeuvre. Outputs and parameter estimations from models are compared to assess the relative performance of the alpha model against its predecessors. The novel alpha model was able to reduce model errors under high positive end-expiratory pressure, resulting in more accurate model outputs. At high positive end-expiratory pressures (20cmH2O), the alpha model had an average error of 11.24%, while the original cardiopulmonary model had a much higher error of 52.21%. Furthermore, identified outputs of the alpha model more closely matched those of the 3 chamber model than the previous cardiopulmonary model. On average, at high positive end-expiratory levels, identified model parameters from the alpha model showed a 6.21% difference to those of the 3 chamber model, while the cardiopulmonary model displayed a 39.43% difference. The alpha model proved to be more stable than the original cardiopulmonary model, making it a good candidate for model based care. However, it produced similar parameter outputs to the simpler three chamber cardiovascular model, bringing into question whether the additional complexity is justified, especially considering the low availability of clinical data in the ICU. There is a critical need for model based care to guide important procedures in ICU, such as fluid therapy. Candidate models should be continuously reviewed in order to guarantee the best possible care. [ABSTRACT FROM AUTHOR]

Background and Objectives Materials and Methods Results Conclusion Blood establishments face environmental, financial, demographic and societal challenges that may impair sustainable blood supply to patients. This study presents the technologies (devices and software) assembled in a global ecosystem implemented by the Blood and Tissue Bank of Aragón (BTBA), Spain, over the last decade to overcome these challenges.Descriptive yearly activity data (2013–2023) of BTBA were retrospectively collected to evaluate the impact of different technologies on blood processing efficiency, focusing on the production of blood components (red blood cell concentrates [RCCs], platelet concentrates [PCs]) and plasma. Operator satisfaction about the technologies introduced in daily routine work was also monitored.Between 2013 and 2023, the annual production decreased by 16.0% for RCCs and increased by 13.3% for PCs. From 2020, all PCs were treated with pathogen reduction technology, and no inventory stock‐out was reported. The lowest PC expiry rate (0.2%) was observed after the implementation of the software for blood processing and PC stock management. The deployment of this software also improved plasma recovery: on average, an extra plasma volume of 9 mL was collected per donation in 2023 compared to 2015. A survey confirmed staff satisfaction.The progressive implementation of automated and software‐based solutions was key to increasing efficiencies in BTBA. This enabled the optimization of blood processing by maximizing productivity, enhancing traceability, reducing overproduction and wastage and increasing the yield of recovered plasma, while ensuring blood product safety and staff satisfaction. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common in cirrhotic patients, especially in the intensive care unit (ICU), and is often associated with poor prognosis. Albumin is often used for plasma volume expansion, but its efficacy in cirrhotic patients with AKI [excluding hepatorenal syndrome (HRS)] is debated. This study aimed to assess the impact of albumin therapy on prognosis in ICU patients with cirrhosis and non-HRS AKI. Methods: A retrospective analysis was conducted using the MIMIC-IV 2.2 database. The primary endpoint was 28-day mortality. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics between the albumin and non-albumin groups. Results: A total of 1,623 patients were included, with 586 receiving albumin. After IPTW, the sample sizes were 1,713 in the non-albumin group and 1,490 in the albumin group. Albumin administration was associated with higher rates of AKI recovery at 48 h but did not improve 28-daymortality in the overall cohort. Further analysis revealed that using 5% albumin concentration was associated with improved 28-day mortality (HR 0.68; 95% CI 0.49-0.95; p = 0.025), whereas 25% albumin did not show benefit. In patients with high bilirubin levels, albumin treatment significantly reduced 28-day mortality. However, albumin therapy may increase 28-day mortality in certain subgroups, including patients with chronic kidney disease and baseline albumin levels >3.3 g/dL. Conclusion: Although albumin therapy improved 28-day mortality in some cases, it may also increase mortality in certain subgroups. The use of albumin in critically ill patients with cirrhosis and AKI should be approached with greater consideration of its risks and benefits. [ABSTRACT FROM AUTHOR]

Normal pressure hydrocephalus (NPH) is associated with a reduction in cerebral blood flow and an ischemic metabolic state. Ischemia should exhaust the available autoregulation in an attempt to correct the metabolic imbalance. There is evidence of some retained autoregulation reserve in NPH. The aim of this study is to model the cerebral autoregulation in NPH to discover a solution to this apparent paradox. A lumped parameter model was developed utilizing the known limits of autoregulation in man. The model was tested by predicting the cerebral blood volume changes which would be brought about by changes in resistance. NPH and the post shunt state were then modeled using the known constraints provided from the literature. The model successfully predicted the cerebral blood volume changes brought about by altering the cerebral perfusion pressure to the limit of autoregulation. The model suggests that NPH is associated with a balanced increase in resistance within the arterial and venous outflow segments. The arterial resistance decreased after modelling shunt insertion. The model suggests that the cerebral blood flow is actively limited in NPH by arteriolar constriction. This may occur to minimize the rise in ICP by reducing the apparent CSF formation rate. [ABSTRACT FROM AUTHOR]

Physiologically Based Pharmacokinetic (PBPK) models can provide forecasts of the drug residues within the organism. Ractopamine (RAC) is a typical β-agonist. In this study, we developed a PBPK model for RAC in goats. The goal was to predict the distribution of the drug after multiple oral administrations. The preliminary PBPK model for RAC in goats performed well in predicting the drug's distribution in most tissues. In our sensitivity analysis, we found that the parameter of Qclu (Blood Flow Volume through Lungs) had the greatest impact on the RAC concentrations in plasma, liver, and kidney and was the most sensitive parameter. Furthermore, our study aimed to assess the withdrawal time (WT) of RAC in different tissues after RAC long-term exposure in goats. We found that the WT of RAC in the kidney was the longest, lasting for 13 days. Overall, the insights gained from this study have important implications for optimizing drug administration in goats and ensuring appropriate withdrawal times to prevent any potential risks. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of a repeated-sprint training in hypoxia induced by voluntary hypoventilation at low lung volume (RSH-VHL) including end-expiratory breath holding (EEBH) of maximal duration. Methods: Over a 4-week period, twenty elite judo athletes (10 women and 10 men) were randomly split into two groups to perform 8 sessions of rowing repeated-sprint exercise either with RSH-VHL (each sprint with maximal EEBH) or with unrestricted breathing (RSN, 10-s sprints). Before (Pre-), 5 days after (Post-1) and 12 days after (Post-2) the last training session, participants completed a repeated-sprint ability (RSA) test on a rowing ergometer (8 × 25-s "all-out" repetitions interspersed with 25 s of passive recovery). Power output (PO), oxygen uptake, perceptual-motor capacity (turning off a traffic light with a predetermined code), cerebral (Δ[Hbdiff]) and muscle (Δ[Hb/Mb]diff) oxygenation, cerebral total haemoglobin concentration (Δ[THb]) and muscle total haemoglobin/myoglobin concentration (Δ[THb/Mb]) were measured during each RSA repetition and/or recovery period. Results: From Pre-to Post-1 and Post-2, maximal PO, mean PO (MPO) of the first half of the test (repetitions 1-4), oxygen uptake, end-repetition cerebral Δ[Hbdiff] and Δ[THb], end-repetition muscle Δ[Hb/Mb]diff and Δ[THb/Mb] and perceptualmotor capacity remained unchanged in both groups. Conversely, MPO of the second half of the test (repetitions 5-8) was higher at Post-1 than at Pre-in RSHVHL only (p < 0.01), resulting in a lower percentage decrement score over the entire RSA test (20.4% ± 6.5% vs. 23.9% ± 7.0%, p = 0.01). Furthermore, MPO (5-8) was greater in RSH-VHL than in RSN at Post-1 (p = 0.04). These performance results were accompanied by an increase in muscle Δ[THb/Mb] (p < 0.01) and a concomitant decrease in cerebral Δ[THb] (p < 0.01) during the recovery periods of the RSA test at Post-1 in RSH-VHL. Conclusion: Four weeks of RSH-VHL including maximal EEBH improved the ability of elite judo athletes to repeat high-intensity efforts. The performance improvement, observed 5 days but not 12 days after training, may be due to enhanced muscle perfusion. The unchanged oxygen uptake and the decrease in cerebral regional blood volume observed at the same time suggest that a blood volume redistribution occurred after the RSH-VHL intervention to meet the increase in muscle perfusion. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer stands as one of the most prevalent malignancies globally, conventional endoscopic specimens have been the primary means of diagnosing preoperative gastric histopathology, however, their limitations in capturing intra-tumor heterogeneity compromise their efficacy in evaluating angiogenesis. Perfusion Computed Tomography (P-CT) emerges as a pivotal functional imaging modality, facilitating objective assessment of tissue perfusion, serving as a marker of angiogenesis. So, our research objective was to evaluate the efficacy of CT perfusion imaging in the prediction of histological grades of gastric tumors using quantitative perfusion parameters such as permeability surface (PS), blood flow (BF), mean transient time (MTT), and blood volume (BV), in addition to the qualitative scoring system then comparing the findings with the histopathological results. Results: PS and BF were statistically significant predictors of the grade of differentiation, their odds ratio (OR) was (1.05, 95% CI 1.02–1.09, for each of them) (P = 0.004, P = 0.009, respectively). MTT also emerged as a significant predictor of the grade of differentiation with an OR of 0.76 (95% CI 0.57–0.93, P = 0.025). Using multivariate logistic regression model, PS was the most potent individual P-CT predictor of differentiation of the grade and the diagnosis of poorly differentiated tumors at ≥ 39 mL/100 g/min cut off point, followed by BF at ≥ 82.2 mL/100 g/min, and MTT at < 8.4 s. Regarding the qualitative scoring system P-CT, poorly differentiated tumors generally received higher scores of PS (P < 0.001), BF (P < 0.001), and BV (P = 0.017), than well and moderately differentiated tumors, however, MTT showed that poorly differentiated tumors were more frequently scored as low compared to well and moderately differentiated tumors (P < 0.001). Conclusions: P-CT is an innovative, non-invasive biomarker for predicting gastric cancer grade by quantitative and qualitative assessment by P-CT parameters (PS, BF and MTT) with particular role of PS as the strongest individual P-CT predictor of differentiation grade followed by BF and MTT at specific cut off points. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Wearable nonelectroencephalographic biosignal recordings captured from the wrist offer enormous potential for seizure monitoring. However, signal quality remains a challenging factor affecting data reliability. Models trained for seizure detection depend on the quality of recordings in peri‐ictal periods in performing a feature‐based separation of ictal periods from interictal periods. Thus, this study aims to investigate the effect of epileptic seizures on signal quality, ensuring accurate and reliable monitoring.This study assesses the signal quality of wearable data during peri‐ictal phases of generalized tonic–clonic and focal to bilateral tonic–clonic seizures (TCS), focal motor seizures (FMS), and focal nonmotor seizures (FNMS). We evaluated accelerometer (ACC) activity and the signal quality of electrodermal activity (EDA) and blood volume pulse (BVP) data. Additionally, we analyzed the influence of peri‐ictal movements as assessed by ACC (ACC activity) on signal quality and examined intraictal subphases of focal to bilateral TCS.We analyzed 386 seizures from 111 individuals in three international epilepsy monitoring units. BVP signal quality and ACC activity levels differed between all seizure types. We found the largest decrease in BVP signal quality and increase in ACC activity when comparing the ictal phase to the pre‐ and postictal phases for TCS. Additionally, ACC activity was strongly negatively correlated with BVP signal quality for TCS and FMS, and weakly for FNMS. Intraictal analysis revealed that tonic and clonic subphases have the lowest BVP signal quality and the highest ACC activity.Motor elements of seizures significantly impair BVP signal quality, but do not have significant effect on EDA signal quality, as assessed by wrist‐worn wearables. The results underscore the importance of signal quality assessment methods and careful selection of robust modalities to ensure reliable seizure detection. Future research is needed to explain whether seizure detection models' decisions are based on signal responses induced by physiological processes as opposed to artifacts. [ABSTRACT FROM AUTHOR]

Purpose: Elite swimmers often schedule altitude training camps ahead of major events in an attempt to maximize performance. However, the relationships between altitude-induced hematological changes, markers of training adaptation, and performance changes in such context are unclear. This study assessed hematological status, markers of daily adaptation, and swimming performance in elite middle-distance and distance swimmers during a 22-day altitude training camp at 2,320 m, 2 weeks prior to World Championship qualification competition. Methods: Venous blood was obtained and total hemoglobin mass (tHbmass) measured (CO rebreathing) in 7 elite swimmers (4 females, 3 males) 8 days before and on day 22 of the altitude camp. Resting heart rate, peripheral oxygen saturation, urinary specific gravity, body mass, fatigue and self-reported sleep duration and quality were monitored daily during the altitude camp. Swimming performance was assessed through a standardized set (6 sets of 4 maximal repetitions of 100 m front crawl) on days 3, 10 and 17 of the camp, and at sea level competitions (200 m-1,500 m) immediately after the camp, and 2 weeks later. Results: tHbmass (+5.6 ± 3.3%; range: 2.1%-11.0%; p < 0.05), red blood cell count, hemoglobin concentration, hematocrit increased at the end of the training camp (p < 0.05). Performance at altitude improved throughout the camp (+1.4 ± 0.4%; range: 0.7%-2.5%; p < 0.05). No significant relationship was noted between hematological changes, the change in altitude performance and any of the monitored daily markers of adaptation during the camp. Compared to the swimmers' previous personal best, competition performances did not improve immediately (2.5% ± 1.9% slower times) and 2 weeks after altitude (1.2% ± 1.4% slower times). Conclusion: The 22-day altitude training camp at 2,320 m was beneficial for elite swimmers' tHbmass, hematological status and performance at altitude, but these benefits did not clearly translate into enhanced sea level performance immediately after or 2 weeks later. The present study confirms the large inter-individual variability in hematological responses to altitude training, and that the improvement in performance at altitude and sea level may depend on factors other than the increase in tHbmass alone. [ABSTRACT FROM AUTHOR]

Background: Peripheral blood‐derived hematopoietic stem cells (HSCs) are widely used for various adult stem cell transplants. To obtain sufficient HSCs from healthy volunteer donors during the apheresis process and ensure that the donors are exposed to fewer apheresis‐related side effects, calculation methods have been developed for the prediction of processed blood volume or CD34+ count. However, there is no consensus on a formula to predict the volume of blood to be processed or the number of stem cells to be obtained. Objective: This study aimed to estimate the predicted blood volume and CD34+ cell counts using collection efficiency (CE)‐based formulas and evaluate their accuracy compared to the actual CD34+ cell counts. It also seeks to identify the factors that affect CE. Methods: Data from 397 healthy, unrelated stem cell donors were retrospectively analyzed. An algorithm using four different CE2 metrics (1st quartile, mean, 3rd quartile, and median) was developed to predict the volume of blood to be processed using the Spectra Optia continuous mononuclear cell collection procedure. Results: When employing the mean CE2 algorithm, the results revealed a strong correlation (r =.894, p <.001) between predicted and actual CD34+ values. The study also identified strong associations between pre‐apheresis CD34+, pre‐apheresis leukocyte count, the use of two doses of G‐CSF, and low CE2. Conclusion: These findings suggest that the mean CE2 algorithm could be a potent, straightforward, and accurate tool for predicting CD34+ stem cell counts in healthy allogeneic stem cell donors and potentially optimizing stem cell collection procedures. [ABSTRACT FROM AUTHOR]

Introduction: Optimization of ultrafiltration during hemodialysis is a critical parameter in achieving therapeutic efficacy and ensuring hemodynamic stability. While various modalities such as blood volume monitoring, inferior vena cava diameter assessment, natriuretic peptide levels, bioimpedance assay, and lung ultrasound have been widely explored in the context of maintenance hemodialysis, the concept of volume‐guided ultrafiltration in dialysis patients with acute kidney injury remains unexplored. Methods: Adult patients with acute kidney injury requiring dialysis, who were hemodynamically stable and not on ventilator support, without underlying lung pathology or cardiac failure, were randomized into two groups. All patients underwent 28‐zone lung ultrasound before dialysis. The ultrafiltration was decided based on the treating physician's clinical judgment in controls. In the intervention group, the ultrafiltration orders prescribed by the treating physician were modified, based on the Kerley B line scores obtained by lung ultrasound. The rest of the dialysis prescriptions were similar. A postdialysis lung ultrasound was done in both groups to assess the postdialysis volume status 30 min after the dialysis session. Results: A total of 74 patients undergoing hemodialysis for acute kidney injury were randomized. The baseline characteristics were comparable except for higher baseline B line score scores in the intervention arm. All patients received similar dialysis prescriptions. The lung ultrasound‐guided ultrafiltration arm had a higher change in B line scores (BLS) from baseline (4 [0–9.5] vs. 0 [0–4]; p value 0.004) during the first dialysis session. The predialysis BLS indexed to ultrafiltration (mL/kbw/h) were significantly lower in controls, reflecting a relatively higher rate of ultrafiltration in controls compared with intervention (p = 0.006). The total number of dialysis sessions done in the control and intervention arm were 61 and 59, respectively. Among controls, 23/61 sessions (37.7%) had intradialytic adverse events, whereas, in the intervention arm, only 4/59 sessions (6.7) had any adverse intradialytic events (p < 0.01). Conclusion: Lung ultrasound‐guided ultrafiltration was associated with a better safety profile, as demonstrated by reduced intradialytic events. [ABSTRACT FROM AUTHOR]

Introduction: Estimated blood loss (EBL) is an important part of the perioperative process. This project aims to determine the accuracy of perioperative team members to estimate blood volume on drapes and the operating room floor. Methods: Aliquots of unused human blood were used to create surgical scenarios, and standardized pictures and videos were taken. Physicians, residents, nurses, medical students, and surgical technicians were surveyed and asked to estimate the blood volume for each series. Accuracy and consistency of responses was analyzed. Results: One hundred and forty five responses were recorded: 57 attending physicians, 36 residents, 27 registered nurses, 17 medical students, and seven circulating surgical techs. Median percent error (PE) for all cases was 211.11%, demonstrating a global overestimation of blood volume. PE for the 150 mL images was statistically significantly lower than that of the 50 and 100 mL images. Circulating Surgical Technicians were the most accurate group, with a median PE of 125%, followed closely by Medical Students (PE = 158.33%). The most accurate specialty was Orthopedics (PE = 168.06%). The least accurate groups were Attending Physicians (PE = 286.11%) and General surgery (GSGY) (PE = 327.78%). The most accurate orthopedic surgery and GSGY subspecialties were Hand (PE = 237.64%) and Vascular (PE = 108.33%), respectively. Statistical analyses showed no significant differences by clinical role, surgical specialty, or subspecialty. Conclusion: This study demonstrates a global overestimation of blood volume when using the visual method, with improved accuracy at higher volumes. Our findings highlight the limitations of visual estimation methods for EBL. [ABSTRACT FROM AUTHOR]

Intravenous volume loading is a common treatment when hypovolemia is a potential cause of oliguria. We studied whether the effectiveness of Ringer's solution and 20% albumin in inducing diuresis differs depending on the mean arterial pressure (MAP). For this purpose, volume kinetic analysis was performed based on urine output and hemoglobin‐derived plasma dilution obtained during and after 136 infusions of Ringer and 85 infusions of 20% albumin. Covariance analysis quantified the diuretic response at different arterial pressures. The results show that the diuretic response to a known plasma volume expansion was greater for Ringer's solution above a MAP of 70 mmHg, while 20% albumin was significantly more effective at lower pressures (p < 0.03). Simulations of the urinary output in response to infusion of a predefined fluid volume yielded superior efficacy for 20% albumin when the MAP was low, while Ringer's was similarly effective when the MAP averaged 100 mmHg. In conclusion, urine output in response to plasma volume expansion with 20% albumin was similar to, or even stronger, than that of Ringer's solution when the MAP was below 70 mmHg. [ABSTRACT FROM AUTHOR]

Background and Objectives: Neonatal cardiac surgery requires careful consideration of cardiopulmonary bypass (CPB) priming fluid composition due to small blood volume and immature physiology. This study investigated the impact of allogeneic stored red blood cells (RBCs) processed using an autotransfusion system in CPB priming fluid for neonates. Materials and Methods: We compared perioperative parameters, inflammatory mediators, coagulation indicators, vasoactive‐inotropic score (VIS) and clinical outcomes between neonates receiving unwashed (n = 56) and washed (n = 45) RBCs in CPB priming fluid. Regression models were used to assess the independent association between RBC washing and patient outcomes. Results: The autotransfusion system improved stored RBC quality. The washed group showed higher peak haematocrit (p < 0.01) and haemoglobin levels (p = 0.04) during CPB, an increased oxygen delivery index during rewarming (p < 0.05) and lower postoperative lactate levels and VIS (p < 0.05). Inflammatory (IL‐6, IL‐8 and IL‐10) and coagulation parameters (D‐dimer, fibrinogen and fibrin degradation product) fluctuated compared with baseline but did not significantly differ between groups. The washed group had a lower incidence of hyperlactacidaemia and delayed sternal closure at CPB weaning. Conclusions: Adding washed allogeneic stored RBCs to neonatal CPB priming fluid reduced postoperative lactate elevation and VIS without early improvement in the inflammatory and coagulation systems. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading indirect cause of maternal morbidity and mortality, accounting for nearly one third of maternal deaths during pregnancy. The burden of cardiovascular disease in pregnancy is increasing, as are the incidence of maternal morbidity and mortality. Normal physiologic adaptations to pregnancy, including increased cardiac output and plasma volume, may unmask cardiac conditions, exacerbate previously existing conditions, or create de novo complications. It is important for care providers to understand the normal physiologic changes of pregnancy and how they may impact the care of patients with cardiovascular disease. This review outlines the physiologic adaptions during pregnancy and their pathologic implications for some of the more common cardiovascular conditions in pregnancy. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate whether liver compression (LC) could increase stroke volume (SV) by more than 15% in healthy, anesthetized dogs with hypovolemia and suggest LC as a novel method to evaluate fluid responsiveness. ANIMALS 6 healthy Beagles. METHODS This prospective, nonrandomized experimental study was conducted from November 2023 to February 2024. The dogs were anesthetized with isoflurane and mechanically ventilated under neuromuscular blockade. After instrumentation, the dogs underwent the following 4 experimental stages in a sequential, nonrandomized manner: stage 1, baseline; stage 2, 30% withdrawal of circulating blood volume; stage 3, 50% infusion of the collected blood; and stage 4, the remaining 50% infusion of the collected blood. At each stage, SV via pulmonary artery thermodilution and hemodynamic variables were measured before, during, and after the LC. RESULTS In stage 2, LC significantly increased mean SV by 30%, from 6.9 to 9 mL/beat. Simultaneously, LC significantly increased mean arterial pressure by 11 mm Hg and mean central venous pressure by 2 mm Hg, while pulse pressure variation significantly decreased from 28% to 22%. In stages 1, 3, and 4, LC did not significantly change mean SV, mean arterial pressure, and pulse pressure variation; however, mean central venous pressure significantly increased during stage 3. CLINICAL RELEVANCE This study demonstrates that LC at 22 mm Hg for 1 minute could increase SV more than 15% in anesthetized, hypovolemic dogs and LC could be used as a novel method to evaluate fluid responsiveness. [ABSTRACT FROM AUTHOR]

Purpose: Spatial intratumoral heterogeneity poses a significant challenge for accurate response assessment in glioblastoma. Multimodal imaging coupled with advanced image analysis has the potential to unravel this response heterogeneity. Methods: Based on automated tumor segmentation and longitudinal registration with follow-up imaging, we categorized contrast-enhancing voxels of 61 patients with suspected recurrence of glioblastoma into either true tumor progression (TP) or pseudoprogression (PsP). To allow the unbiased analysis of semantically related image regions, adjacent voxels with similar values of cerebral blood volume (CBV), FET-PET, and contrast-enhanced T1w were automatically grouped into supervoxels. We then extracted first-order statistics as well as texture features from each supervoxel. With these features, a Random Forest classifier was trained and validated employing a 10-fold cross-validation scheme. For model evaluation, the area under the receiver operating curve, as well as classification performance metrics were calculated. Results: Our image analysis pipeline enabled reliable spatial assessment of tumor response. The predictive model reached an accuracy of 80.0% and a macro-weighted AUC of 0.875, which takes class imbalance into account, in the hold-out samples from cross-validation on supervoxel level. Analysis of feature importances confirmed the significant role of FET-PET-derived features. Accordingly, TP- and PsP-labeled supervoxels differed significantly in their 10th and 90th percentile, as well as the median of tumor-to-background normalized FET-PET. However, CBV- and T1c-related features also relevantly contributed to the model's performance. Conclusion: Disentangling the intratumoral heterogeneity in glioblastoma holds immense promise for advancing precise local response evaluation and thereby also informing more personalized and localized treatment strategies in the future. [ABSTRACT FROM AUTHOR]

During pregnancy an increased cardiac output (Q̇$\dot{Q}$) and blood volume (BV) occur to support fetal growth. Increased Q̇$\dot{Q}$ and BV also occur during chronic endurance exercise training and benefit performance. We investigated if sprint interval training (SIT) undertaken early postpartum maintains the elevated Q̇$\dot{Q}$ and BV of pregnancy and benefits performance. The participant, a competitive field hockey player and former cyclist, visited our laboratory at 2 weeks of gestation (baseline) and postpartum pre‐, mid‐ and post‐intervention (PPpre, PPmid and PPpost). Delivery was uncomplicated and she felt ready to start the SIT programme 5 weeks postpartum. Inert gas rebreathing was used to measure peak exercise Q̇$\dot{Q}$ (Q̇$\dot{Q}$peak); V̇O2peak${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ was measured with a metabolic cart; and postpartum haematological values were measured with carbon monoxide rebreathing. The 18 SIT sessions progressed from four to eight sprints at 130% of V̇O2peak${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ peak power output. Q̇$\dot{Q}$peak increased from baseline at all postpartum time points (baseline 16.2 vs. 17.5, 16.8 and 17.2 L/min at PPpre, PPmid and PPpost, respectively). Relative V̇O2peak${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ remained below baseline values at all postpartum measurements (baseline 44.9 vs. 41.0, 42.3 and 42.5 mL/kg/min at PPpre, PPmid and PPpost, respectively) whereas absolute V̇O2peak${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ rapidly reached baseline values postpartum (baseline 3.19 vs. 3.12, 3.23 and 3.18 L/min at PPpre, PPmid and PPpost, respectively). Postpartum BV (5257, 4271 and 5214 mL at PPpre, PPmid and PPpost, respectively) and Hbmass (654, 525 and 641 g at PPpre, PPmid and PPpost, respectively) were similar between PPpre and PPpost but decreased alongside Q̇$\dot{Q}$peak at PPmid. Peak power was returned to pre‐pregnancy values by intervention end (302 vs. 303 W, baseline vs. PPpost). These findings show that SIT undertaken early postpartum defends the elevated Q̇$\dot{Q}$peak of pregnancy and rapidly returns absolute V̇O2peak${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ and peak power to baseline levels. What is the central question of this study?Can the enhanced cardiac output of pregnancy be maintained with strenous exercise training undertaken early postpartum.What is the main finding and its importance?Baseline values of absolute oxygen consumption, peak power output and peak exercise cardiac output can be regained rapidly or surpassed following 6 weeks of sprint interval training postpartum. Sprint interval training can be used by endurance trained females to safely resume training early postpartum, allowing a rapid and efficient return to baseline fitness levels. [ABSTRACT FROM AUTHOR]

Detection of circulating tumor DNA (ctDNA) via whole-genome sequencing (WGS) in patients with muscle-invasive bladder cancer has great clinical potential for prognostication, monitoring of treatment responses, and early detection of minimal residual disease and recurrence. A tumor-informed WGS-based ctDNA detection strategy is highly suitable for clinical implementation because of the low input requirements and simple laboratory workflow. Circulating tumor DNA (ctDNA) can be used for sensitive detection of minimal residual disease (MRD). However, the probability of detecting ctDNA in settings of low tumor burden is limited by the number of mutations analyzed and the plasma volume available. We used a whole-genome sequencing (WGS) approach for ctDNA detection in patients with urothelial carcinoma. We used a tumor-informed WGS approach for ctDNA-based detection of MRD and evaluation of treatment responses. We analyzed 916 longitudinally collected plasma samples from 112 patients with localized muscle-invasive bladder cancer who received neoadjuvant chemotherapy (NAC) before radical cystectomy. Recurrence-free survival (primary endpoint), overall survival, and ctDNA dynamics during NAC were assessed. We found that WGS-based ctDNA detection is prognostic for patient outcomes with a median lead time of 131 d over radiographic imaging. WGS-based ctDNA assessment after radical cystectomy identified recurrence with sensitivity of 91% and specificity of 92%. In addition, genomic characterization of post-treatment plasma samples with a high ctDNA level revealed acquisition of platinum therapy–associated mutational signatures and copy number variations not present in the primary tumors. The sequencing depth is a limitation for studying tumor evolution. Our results support the use of WGS for ultrasensitive ctDNA detection and highlight the possibility of plasma-based tracking of tumor evolution. WGS-based ctDNA detection represents a promising option for clinical use owing to the low volume of plasma needed and the ease of performing WGS, eliminating the need for personalized assay design. [ABSTRACT FROM AUTHOR]

Background: We examined whether the time to positivity (TTP) and growth and detection plot graph (GDPG) created by the automated blood culture system can be used to determine the bacterial load in bacteremic patients and its potential association correlation with disease severity. Methods: Known bacterial inocula were injected into the blood culture bottles. The GDPGs for the specific inocula were downloaded and plotted. A cohort of 30 consecutive clinical cultures positive for S. aureus and E. coli was identified. Bacterial load was determined by comparing the GDPG with the "standard" curves. Variables associated with disease severity were compared across 3 bacterial load categories (< 100, 100–1000, > 1000 CFU/mL). Results: S. aureus growth was sensitive to the blood volume obtained whereas E. coli growth was less so. A 12-hour delay in sample transfer to the microbiology laboratory resulted in a decrease in TTP by 2–3 h. Mean TTP was 15 and 10 h for S. aureus and E. coli, respectively, which correlates with > 1000 CFU/mL and 500–1000 CFU/ml. For S. aureus, patients with a bacterial load > 100 CFU/mL had a higher mortality rate, (OR for death = 9.7, 95% CI 1.6–59, p = 0.01). Bacterial load > 1000 CFU/mL had an odds ratio of 6.4 (95% CI1.2-35, p = 0.03) to predict an endovascular source. For E. coli bacteremia, we did not find any correlations with disease severity. Conclusion: GDPG retrieved from the automated blood culture system can be used to estimate bacterial load. S.aureus bacterial load, but not E.coli, was associated with clinical outcome. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest increased abdominal girth in obese individuals provides a "cushion effect," against severe abdominal trauma. In comparison, the unique anatomic/physiological condition of pregnancy, such as the upward displacement of organs by an expanding uterus, may decrease risk of abdominal injury. However, increased overall blood volume and vascularity of organs during pregnancy raise concerns for increased bleeding and potentially more severe injuries. Therefore, this study aimed to elucidate whether the "cushion effect" observed in obese patients extends to pregnant trauma patients (PTPs). We hypothesized a lower risk of blunt solid organ injury (BSOI) (liver, spleen, and kidney) in pregnant vs non-pregnant blunt trauma patients. Methods: The 2020-2021 Trauma Quality Improvement Program was queried for all female blunt trauma patients (age<50 years) involved in motor vehicle collisions (MVCs). We compared pregnant vs non-pregnant patients. The primary outcomes were incidence of BSOI, and severity of abdominal trauma defined by abbreviated injury scale (AIS). Results: From 94,831 female patients, 2598 (2.7%) were pregnant. When compared to non-pregnant patients, PTPs had lower rates of liver (5.5% vs 7.6%, P < .001) and kidney (1.8% vs 2.6%, P = .013) injury. However, PTPs had higher rates of serious (13.4% vs 9.0%, P < .001) and severe abdominal injury (7.5% vs 4.3%, P < .001). Discussion: BSOI occurred at a lower rate in PTPs compared to non-PTPs; however, contrary to the "cushion effect" observed in obese populations, pregnant women had a higher rate of severe abdominal injuries. These data support comprehensive evaluations for PTPs presenting after a MVC. Level of Evidence: IV (therapeutic). [ABSTRACT FROM AUTHOR]

Background and aims: The placement of Transjugular intrahepatic portosystemic shunt (TIPS) results in a sudden increase in central circulating blood volume, which requires proper regulation of the cardiovascular system. We aimed to investigate the impact of TIPS on cirrhotic cardiomyopathy (CCM). Method: A consecutive case series of patients with cirrhosis who underwent TIPS were evaluated by echocardiography and pressure measurements before, immediately after TIPS and 2–4 days later (delayed). Furthermore, all patients underwent a one-year follow-up. Results: In this study, 107 patients were enrolled, 38 (35.5%) with CCM. Echocardiography revealed an increase in postoperative left ventricular filling pressure accompanied by an elevation in left ventricular ejection fraction (LVEF). However, patients in the CCM group exhibited lower LVEF and mean arterial pressure (MAP) compared to the non-CCM group. Post-TIPS, CCM patients showed increased right atrium pressure (RAP) that normalized within 2–4 days, whereas non-CCM patients had lower RAP than baseline. Compared to patient without CCM, CCM patients revealed lower immediate (16.7 ± 4.4 vs. 18.9 ± 4.8, p = 0.022) and delayed 15.9 ± 3.7 vs. 17.7 ± 5.3, p = 0.044) portal vein pressures (PVP) and portal pressure gradients (PPG) (7.7 ± 3.4 vs. 9.2 ± 3.6, p = 0.032 and 10.1 ± 3.1 vs. 12.3 ± 4.9, p = 0.013). The 1-year mortality rates were 13.2% for CCM patients and 4.3% for non-CCM patients (log-rank test, p = 0.093), with MELD score, and preoperative RAP significantly associated with the mortality. Conclusion: Cirrhotic patients with CCM exhibit lower PVP and PPG immediately after TIPS and 2–4 days later, without significantly impacting one-year survival outcomes. [ABSTRACT FROM AUTHOR]

Multi-echo, multi-contrast methods are increasingly used in dynamic imaging studies to simultaneously quantify R 2 ∗ and R 2. To overcome the computational challenges associated with nonlinear least squares (NLSQ) fitting, we propose a generalized linear least squares (LLSQ) solution to rapidly fit R 2 ∗ and R 2. Spin- and gradient-echo (SAGE) data were simulated across T 2 ∗ and T 2 values at high (200) and low (20) SNR. Full (four-parameter) and reduced (three-parameter) parameter fits were implemented and compared with both LLSQ and NLSQ fitting. Fit data were compared to ground truth using concordance correlation coefficient (CCC) and coefficient of variation (CV). In vivo SAGE perfusion data were acquired in 20 subjects with relapsing-remitting multiple sclerosis. LLSQ R 2 ∗ and R 2 , as well as cerebral blood volume (CBV), were compared with the standard NLSQ approach. Across all fitting methods, T 2 ∗ was well-fit at high (CCC = 1, CV = 0) and low (CCC ≥ 0.87, CV ≤ 0.08) SNR. Except for short T 2 ∗ values (5–15 ms), T 2 was well-fit at high (CCC = 1, CV = 0) and low (CCC ≥ 0.99, CV ≤ 0.03) SNR. In vivo, LLSQ R 2 ∗ and R 2 estimates were similar to NLSQ, and there were no differences in R 2 ∗ across fitting methods at high SNR. However, there were some differences at low SNR and for R 2 at high and low SNR. In vivo NLSQ and LLSQ three parameter fits performed similarly, as did NLSQ and LLSQ four-parameter fits. LLSQ CBV nearly matched the standard NLSQ method for R 2 ∗ - (0.97 ratio) and R 2 -CBV (0.98 ratio). Voxel-wise whole-brain fitting was faster for LLSQ (3–4 min) than NLSQ (16–18 h). LLSQ reliably fit for R 2 ∗ and R 2 in simulated and in vivo data. Use of LLSQ methods reduced the computational demand, enabling rapid estimation of R 2 ∗ and R 2. [ABSTRACT FROM AUTHOR]

Purpose: To introduce a simple system exploitation with the potential to turn MRI scanners into general‐purpose radiofrequency (RF) motion monitoring systems. Methods: Inspired by Pilot Tone (PT), this work proposes Beat Pilot Tone (BPT), in which two or more RF tones at arbitrary frequencies are transmitted continuously during the scan. These tones create motion‐modulated standing wave patterns that are sensed by the receiver coil array, incidentally mixed by intermodulation in the receiver chain, and digitized simultaneously with the MRI data. BPT can operate at almost any frequency as long as the intermodulation products lie within the bandwidth of the receivers. BPT's mechanism is explained in electromagnetic simulations and validated experimentally. Results: Phantom and volunteer experiments over a range of transmit frequencies suggest that BPT may offer frequency‐dependent sensitivity to motion. Using a semi‐flexible anterior receiver array, BPT appears to sense cardiac‐induced body vibrations at microwave frequencies (≥$$ \ge $$1.2 GHz). At lower frequencies, it exhibits a similar cardiac signal shape to PT, likely due to blood volume changes. Other volunteer experiments with respiratory, bulk, and head motion show that BPT can achieve greater sensitivity to motion than PT and greater separability between motion types. Basic multiple‐input multiple‐output (4×22$$ 4\times 22 $$ MIMO) operation with simultaneous PT and BPT in head motion is demonstrated using two transmit antennas and a 22‐channel head‐neck coil. Conclusion: BPT may offer a rich source of motion information that is frequency‐dependent, simultaneous, and complementary to PT and the MRI exam. [ABSTRACT FROM AUTHOR]

Purpose: A method is proposed to quantify cerebral blood volume (vb$$ {v}_b $$) and intravascular water residence time (τb$$ {\tau}_b $$) using MR fingerprinting (MRF), applied using a spoiled gradient echo sequence without the need for contrast agent. Methods: An in silico study optimized an acquisition protocol to maximize the sensitivity of the measurement to vb$$ {v}_b $$ and τb$$ {\tau}_b $$ changes. Its accuracy in the presence of variations in T1,t$$ {\mathrm{T}}_{1,t} $$, T1,b$$ {\mathrm{T}}_{1,b} $$, and B1$$ {\mathrm{B}}_1 $$ was evaluated. The optimized protocol (scan time of 19 min) was then tested in a exploratory healthy volunteer study (10 volunteers, mean age 24 ±$$ \pm $$ 3, six males) at 3 T with a repeat scan taken after repositioning to allow estimation of repeatability. Results: Simulations show that assuming literature values for T1,b$$ {\mathrm{T}}_{1,b} $$ and T1,t$$ {\mathrm{T}}_{1,t} $$, no variation in B1$$ {\mathrm{B}}_1 $$, while fitting only vb$$ {v}_b $$ and τb$$ {\tau}_b $$, leads to large errors in quantification of vb$$ {v}_b $$ and τb$$ {\tau}_b $$, regardless of noise levels. However, simulations also show that matching T1,t$$ {\mathrm{T}}_{1,t} $$, T1,b$$ {\mathrm{T}}_{1,b} $$, B1+$$ {\mathrm{B}}_1^{+} $$, vb$$ {v}_b $$ and τb$$ {\tau}_b $$, simultaneously is feasible at clinically achievable noise levels. Across the healthy volunteers, all parameter quantifications fell within the expected literature range. In addition, the maps show good agreement between hemispheres suggesting physiologically relevant information is being extracted. Expected differences between white and gray matter T1,t$$ {\mathrm{T}}_{1,t} $$ (p < 0.0001) and vb$$ {v}_b $$ (p < 0.0001) are observed, T1,b$$ {\mathrm{T}}_{1,b} $$ and τb$$ {\tau}_b $$ show no significant differences, p = 0.4 and p = 0.6, respectively. Moderate to excellent repeatability was seen between repeat scans: mean intra‐class correlation coefficient of T1,t:0.91$$ {\mathrm{T}}_{1,t}:0.91 $$, T1,b:0.58$$ {\mathrm{T}}_{1,b}:0.58 $$, vb:0.90$$ {v}_b:0.90 $$, and τb:0.96$$ {\tau}_b:0.96 $$. Conclusion: We demonstrate that regional simultaneous quantification of vb$$ {v}_b $$, τb$$ {\tau}_b $$, T1,b,T1,t$$ {\mathrm{T}}_{1,b},{T}_{1,t} $$, and B1+$$ {\mathrm{B}}_1^{+} $$ using MRF is feasible in vivo. [ABSTRACT FROM AUTHOR]

Aims: Congestive heart failure (HF) is a common complication in patients with acute myocardial infarction (AMI). The estimated plasma volume status [ePVS = (100 − haematocrit)/haemoglobin] is used as the blood plasma volume index to determine the presence of congestion in patients with HF. However, the clinical impact of ePVS at discharge in patients with AMI remains unclear. This study aimed to investigate whether ePVS at discharge could determine the long‐term prognosis in patients with AMI. Methods and results: We retrospectively identified patients with AMI with ePVS measured at discharge between January 2012 and December 2020. The primary endpoint was post‐discharge all‐cause death. The patients were divided into two groups according to an ePVS cut‐off value of 5.5%, which is commonly used in HF. In total, 1012 patients with AMI were included. The median age was 70 years (range, 61–78 years), and 76.4% of the patients were male. The ePVS > 5.5% (high‐ePVS) group included 365 patients (36.1%), and the all‐cause mortality rate in the total cohort was 17.7%. The log‐rank test revealed that the high‐ePVS group had a significantly higher rate of all‐cause death than the ePVS ≤ 5.5% (low‐ePVS) group (P < 0.001). Multivariate Cox proportional hazards model analysis revealed that high ePVS was associated with post‐discharge all‐cause death, independent of other risk factors (hazard ratio = 1.879; 95% confidence interval = 1.343–2.629, P < 0.001). Conclusions: High ePVS at discharge was independently associated with high post‐discharge all‐cause mortality in patients with AMI. Our study suggests that ePVS at discharge in patients with AMI could serve as a novel prognostic marker. [ABSTRACT FROM AUTHOR]

Introduction: Acute hypertriglyceridemia is considered a category III indication for plasmapheresis. The use of plasma as replacement fluid (RF) has been suggested to replace the consumed lipoprotein lipase. Heparin when used as an anticoagulant could possibly release lipoprotein lipase, thereby increasing triglyceride clearance. Methods: The impact of RF (albumin vs fresh frozen plasma (FFP) and anticoagulant (ACD‐A vs. heparin) on triglycerides following plasmapheresis in 27 patients with severe hypertriglyceridemia (SHTG) was investigated. A paired study of four patients with recurrent SHTG was conducted, evaluating continuous (Optia) versus intermittent flow plasmapheresis (Haemonetics). Results: Shorter procedures positively impacted triglycerides (TG) drop post‐sessions p < 0.05. In albumin sessions, patients who used heparin demonstrated significantly greater drop in TG and required less sessions than did those with citrate p < 0.05. In heparin sessions, patients who used albumin demonstrated significantly greater drop in triglycerides and required less sessions than did those with FFP p < 0.05. Three of six patients who used FFP and heparin showed a triglyceride drop of 11.7% following three sessions and a 50% drop with one albumin session. Compared with Haemonetics, Optia removed comparable volumes of plasma in less time, processing smaller blood volumes and using less citrate p < 0.05. Patients demonstrated significantly lower drop in TG and required more sessions with Haemonetics than they did with Optia p < 0.05. Conclusion: Shorter procedure was the main predictor for effective TG clearance. This can be achieved by continuous apheresis technology, particularly when using albumin as RF. TG removal via Optia seems to be optimized by using heparin. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Ultrafiltration (UF) is an essential process of restoring fluid homeostasis during hemodialysis (HD). Fluid shifts across the extracellular compartments during UF, predominantly across the capillary interface and between the macro‐ and microcirculation. A mismatch between UF and transcapillary fluid transport can lead to hemodynamic instability leading to cardiac morbidity. We wished to study intradialytic fluid transport characteristics and their variation during UF to identify factors that govern variability in transcapillary fluid movement in HD.Twenty‐two patients undergoing stable HD sessions were studied to measure and monitor absolute blood and plasma volume throughout UF. A computational mathematical model of predicted plasma volume decay during UF was analyzed with respect to the intradialytic real‐time data profile. Pre‐ and post‐dialysis fluid status was assessed using multifrequency bioimpedance spectroscopy. Serum electrolytes, osmolality, and total protein concentration were measured pre‐ and post‐dialysis and during the intradialytic phase.Two distinct profiles of PV responses were detected. 60% of the patients presented plasma volume decline, characterized by a high percentage of volume decrease during the first hour, and a subsequent slower decrease with early rebound. The model was modified to achieve a proper fit of these volume profiles, assuming time‐dependent changes in selected parameters governing the refilling flow.Although the modified model could more accurately fit the data, the new parameter values often fell outside of a physiologically acceptable range, suggesting that other factors not included in the classic description of transcapillary fluid transport might be the cause of the observed patterns. [ABSTRACT FROM AUTHOR]

Background: Physiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT). Methods: In this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats. Discussion: The perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma. Trial registration: ClinicalTrials.gov ID: NCT02613988. [ABSTRACT FROM AUTHOR]

AbstractA knowledge of the difference of spatio-temporal behaviour of nanomedicine in different type of tumour models is important to develop well-targeted nanomedicine for tumour. In this study, intratumoral accumulation of the model nanomedicine, gadolinium-conjugated dextran (Gd-Dex), was examined with magnetic resonance imaging in two tumour models; mouse sarcoma S180 and radiation-induced mouse fibrosarcoma RIF-1. From time-course of the distribution images, the plasma-to-tumour interstitial tissue transfer constant (Ktrans) and fractional plasma volume (Vp) were calculated and mapped. Gd-Dex preferentially distributed to the marginal region of S180 tumours immediately after its injection, and then started to accumulate in some parts of the central region. Ktrans and Vp values were large in the marginal region, while only Ktrans was large in some parts of the central region. In contrast, the distribution of Gd-Dex in RIF-1 tumours was fairly homogeneous, and may have resulted from the homogeneous distributions of Ktrans and Vp. The amounts of Gd-Dex that accumulated in entire tumours in both tumour models correlated with the volume of tumours; however, accumulation in large S180 tumours deviated from the correlation in the early phase. The differences in the manner and pharmacokinetics of nanomedicine among tumour models may affect the accumulation of the medicine. [ABSTRACT FROM AUTHOR]

BACKGROUND: Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. This study tested the hypothesis that Dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF. METHODS: In this secondary analysis from the CAMEO-DAPA trial (Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial), 37 patients with HFpEF (mean age 68 ± 9 years, women 65%) underwent invasive hemodynamic exercise testing with simultaneous echocardiography at baseline and following treatment for 24 weeks with Dapagliflozin or placebo. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated from hemodynamic indices fit to a comprehensive cardiovascular model. RESULTS: There was no statistically significant effect of Dapagliflozin on resting BP, but Dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mm Hg [95% CI, -33.9 to -3.7] P=0.016). Reduction in BP was related to improved exertional total arterial compliance (ETD, 0.06 mL/mm Hg/m2 [95% CI, 0.003--0.11] P=0.039) and aortic root characteristic impedance (ETD, -2.6 mm Hg/mL*sec [95% CI: -5.1 to -0.03] P=0.048), with no significant effect on systemic vascular resistance. Dapagliflozin reduced estimated stressed blood volume at rest and during peak exercise (ETD, -292 mm Hg [95% CI, -530 to -53] P=0.018), and improved venous capacitance evidenced by a decline in ratio of estimated stressed blood volume to total blood volume (ETD, -7.3% [95% CI, -13.3 to -1.3] P=0.020). Each of these effects of Dapagliflozin at peak exercise were also observed during matched 20W exercise intensity. Improvements in total arterial compliance and estimated stressed blood volume were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in estimated stressed blood volume during exercise (r=0.40, P=0.019). Decreases in BP were correlated with reduction in pulmonary capillary wedge pressure during exercise (r=0.56, P<0.001). CONCLUSIONS: In patients with HFpEF, treatment with Dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with sodium-glucose cotransporter-2 inhibitors in HFpEF. [ABSTRACT FROM AUTHOR]

ABSTRACT This study explores atmospheric plasma as a novel approach for the degradation of persistent per‐ and polyfluoroalkyl substances (PFAS) in contaminated waters. Using response surface methodology and Box–Behnken design, the performance of the self‐pulsing discharge (SPD) reactor was optimized by adjusting the following independent factors: input power, plasma area‐to‐liquid volume ratio, and argon bubbling time. Optimization was assessed using four specific indicators: kPFOA and G50, for the process velocity and energy efficiency, respectively; kPFOA/kPFHpA and ΣPFAS/C0, both for the presence of PFAS in the treated water for the process products. Under the optimized operating conditions, residual PFAS summed up to only 2.4% of the carbon initially present as PFOA, and a remarkable G50 value of (523 ± 10) mg/kWh was obtained. [ABSTRACT FROM AUTHOR]

This document is a correction to a previously published article on the reliability of pulmonary diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO) during exercise and in different body positions. The correction addresses errors in the reported values of alveolar-capillary membrane diffusing capacity (DM) and pulmonary capillary blood volume (Vc) in the original article. The authors found that the equipment used for measurement reported DM differently than assumed, affecting the Vc estimates. The corrected article suggests that DLNO may be a useful index of alveolar-capillary reserve and that DLNO during exercise or in the supine position should be the preferred outcome measure for investigating this reserve. [Extracted from the article]

The first step in blood testing necessitates blood separation to obtain an adequate volume of plasma. Traditional centrifugation is bulky, expensive and electricity-powered, which is not suitable for micro-scale blood plasma separation in point-of-care testing (POCT) cases. Microfluidic paper-based plasma separation devices present a promising alternative for plasma separation in such occasions. However, they are limited in terms of plasma yield, which hinders analyte detection. Herein, we proposed a humidity-enhanced paper-based microfluidic plasma separation method to address this issue. Specifically, paper was first treated by blood-typing antibodies, then samples of whole blood were introduced into the prepared paper. After waiting for 5 min for RBC agglutination and plasma wicking under high humidity, micro-scale plasma separation from whole blood was achieved. As a result, an extremely high plasma yield of up to 60.1% could be separated from whole blood through using Xuan-paper. Meanwhile, the purity of plasma could reach 99.99%. Finally, this innovative approach was effortlessly integrated into distance-based glucose concentration detection, enabling rapid determination of blood glucose levels through naked-eye observation. Considering the simplicity and inexpensiveness of this method, we believe that this technology could be integrated to more paper-based microfluidic analytical devices for rapid and accurate detection of plasma analytes in POCT. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the first cause of death worldwide and kills more people each year than any other cause of death. N, N-dimethylaniline-heliamine (DH), a synthetic tetrahydroisoquinoline alkaloid, has shown notable antiarrhythmic activity. However, the metabolic processes and pharmacokinetic characteristics of DH in rats have not been studied. This study aims to identify its metabolites, as well as develop and validate a rapid and efficient bioanalytical method for quantifying DH in rat plasma over a wide range of concentrations. Its metabolites were characterized in silico, in vitro, and in vivo. A series of 16 metabolites were identified, of which 12 were phase I metabolites and 4 were phase II metabolites. A low probability of DH binding to DNA, protein, and glutathione is predicted by the in silico model. The main metabolic processes of DH were demethylation, dehydrogenation, glucuronidation, and sulfation. Concentration–time profiles were generated by analyzing the plasma, and the outcomes were analyzed via non-compartmental analysis to identify the pharmacokinetic parameters. Among the detected parameters were the volume of distribution, estimated at 126,728.09 ± 56,867.09 mL/kg, clearance at 30,148.65 ± 15,354.27 mL/h/kg, and absolute oral bioavailability at 16.11%. The plasma distribution volume of DH was substantially higher than the overall plasma volume of rats, which suggests that DH has a specific tissue distribution in rats. This study suggests that DH is appropriately bioavailable and excreted via a variety of routes and has low toxicity. [ABSTRACT FROM AUTHOR]

This narrative review delves into the intricate interplay between the lungs and the kidneys, with a focus on elucidating the pathogenesis of diseases influenced by immunological factors, acid–base regulation, and blood gas disturbances, as well as assessing the effects of various therapeutic modalities on these interactions. Key disorders, such as anti-glomerular basement membrane (anti-GBM) disease, the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and Anti-neutrophil Cytoplasmic Antibodies (ANCA) associated vasculitis (AAV), are also examined to shed light on their underlying mechanisms. This review also explores the relationship between acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), emphasizing how inflammatory mediators can lead to systemic damage and impact multiple organs. In ARDS, fluid overload exacerbates pulmonary edema, while imbalances in blood volume, such as hypovolemia or hypervolemia, can precipitate renal dysfunction. The review highlights how mechanical ventilation strategies can compromise renal blood flow, trigger systemic inflammation, and induce hemodynamic and neurohormonal alterations, all contributing to lung and kidney damage. The impact of extracorporeal membrane oxygenation (ECMO) on lung–kidney interactions is evaluated, highlighting its role in severe respiratory failure and its renal implications. Emerging therapies, such as mesenchymal stem cells and extracellular vesicles, are discussed as promising avenues to mitigate organ damage and enhance outcomes in critically ill patients. Overall, this review offers a nuanced exploration of lung–kidney dynamics, bridging historical insights with contemporary perspectives. It underscores the clinical significance of these interactions in critically ill patients and advocates for integrated management approaches to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Physical exercise and gravitational load affect the activity of the cardiovascular system. How these factors interact with one another is still poorly understood. Here we investigate how the cardiovascular system responds to leg-press exercise during head-down tilt, a posture that reduces orthostatic stress, limits gravitational pooling, and increases central blood volume. Methods: Seventeen healthy participants performed leg-press exercise during head-down tilt at different combinations of resistive force, contraction frequency, and exercise duration (30 and 60's), leading to different exercise power. Systolic (sBP), diastolic (dBP), mean arterial pressure (MAP), pulse pressure (PP) and heart rate (HR) were measured continuously. Cardiovascular responses were evaluated by comparing the values of these signals during exercise recovery to baseline. Mixed models were used to evaluate the effect of exercise power and of individual exercise parameter on the cardiovascular responses. Results: Immediately after the exercise, we observed a clear undershoot in sBP (Δ = -7.78 ± 1.19'mmHg), dBP (Δ = -10.37 ± 0.84'mmHg), and MAP (Δ = -8.85 ± 0.85'mmHg), an overshoot in PP (Δ = 7.93 ± 1.13'mmHg), and elevated values of HR (Δ = 33.5 ± 0.94'bpm) compared to baseline (p < 0.0001). However, all parameters returned to similar baseline values 2'min following the exercise (p > 0.05). The responses of dBP, MAP and HR were significantly modulated by exercise power (correlation coefficients: rdBP = -0.34, rMAP = -0.25, rHR = 0.52, p < 0.001). All signals' responses were modulated by contraction frequency (p < 0.05), increasing the undershoot in sBP (Δ = -1.87 ± 0.98'mmHg), dBP (Δ = -4.85 ± 1.01 and Δ = -3.45 ± 0.98'mmHg for low and high resistive force respectively) and MAP (Δ = -3.31 ± 0.75'mmHg), and increasing the overshoot in PP (Δ = 2.57 ± 1.06'mmHg) as well as the value of HR (Δ = 16.8 ± 2.04 and Δ = 10.8 ± 2.01'bpm for low and high resistive force respectively). Resistive force affected only dBP (Δ = -4.96 ± 1.41'mmHg, p < 0.0001), MAP (Δ = -2.97 ± 1.07'mmHg, p < 0.05) and HR (Δ = 6.81 ± 2.81'bpm, p < 0.0001; Δ = 15.72 ± 2.86'bpm, p < 0.0001; Δ = 15.72 ± 2.86'bpm, p < 0.05, depending on the values of resistive force and contraction frequency), and exercise duration affected only HR (Δ = 9.64 ± 2.01'bpm, p < 0.0001). Conclusion: Leg exercises caused only immediate cardiovascular responses, potentially due to facilitated venous return by the head-down tilt position. The modulation of dBP, MAP and HR responses by exercise power and that of all signals by contraction frequency may help optimizing exercise prescription in conditions of limited orthostatic stress. [ABSTRACT FROM AUTHOR]

Background: Ethyl alcohol (ethanol) consumption is ostensibly known to increase the risk of morbidity and mortality during hot weather and heatwaves. However, how alcohol independently alters physiological, perceptual, and behavioral responses to heat stress remains poorly understood. Therefore, we conducted a systematic scoping review to understand how alcohol consumption affects thermoregulatory responses to the heat. Methods: We searched five databases employing the following eligibility criteria, studies must have: 1) involved the oral consumption of ethanol, 2) employed a randomized or crossover-control study design with a control trial consisting of a volume-matched, non-alcoholic beverage, 3) been conducted in healthy adult humans, 4) reported thermophysiological, perceptual, hydration status markers, and/or behavioral outcomes, 5) been published in English, 6) been conducted in air or water at temperatures of > 28°C, 7) involved passive rest or exercise, and 8) been published before October 4th, 2023. Results: After removing duplicates, 7256 titles were screened, 29 papers were assessed for eligibility and 8 papers were included in the final review. Across the 8 studies, there were a total of 93 participants (93 male/0 female), the average time of heat exposure was 70 min and average alcohol dose was 0.68 g·kg1. There were 23 unique outcome variables analyzed from the studies. The physiological marker most influenced by alcohol was core temperature (lowered with alcohol consumption in 3/4 studies). Additionally, skin blood flow was increased with alcohol consumption in the one study that measured it. Typical markers of dehydration, such as increased urine volume (1/3 studies), mass loss (1/3 studies) and decreased plasma volume (0/2 studies) were not consistently observed in these studies, except for in the study with the highest alcohol dose. Conclusion: The effect of alcohol consumption on thermoregulatory responses is understudied, and is limited by moderate doses of alcohol consumption, short durations of heat exposure, and only conducted in young-healthy males. Contrary to current heat-health advice, the available literature suggests that alcohol consumption does not seem to impair physiological responses to heat in young healthy males. [ABSTRACT FROM AUTHOR]