Physiological Assessment Research Articles

Physiological Assessment of ECCO2R on the Work of Breathing in Exacerbations of COPD

Rationale The impact of extracorporeal carbon dioxide removal (ECCO2R) on work of breathing and aeration in exacerbations of chronic obstructive pulmonary disease (AECOPD) is poorly understood. Objectives The study explores the impact of non-invasive ventilation (NIV) and ECCO2R on respiratory drive, effort and distribution of ventilation in AECOPD. Methods Patients enrolled in a randomised controlled study of the addition of ECCO2R to NIV compared with NIV underwent oesophageal pressure measurement, electrical impedance tomography and parasternal electromyography. Measurements and main results 18 patients were enrolled, nine in each arm. Of these, eight in the NIV arm and seven in the ECCO2R arm underwent physiological assessment. Patients randomised to ECCO2R, had a period of NIV combined with ECCO2R and, after removal of NIV, a period of ECCO2R alone. The removal of NIV whilst remaining on ECCO2R resulted in a respiratory acidosis (pH 7.34 (7.31–7.34) vs. 7.31 (7.31–7.34), p < 0.0001), increased work of breathing (7.43 (6.08–10.19) vs. 11.1 (8.11–15.15) J/min, p < 0.0001) and increased neural drive (884.4 (684.7–967.3) vs. 1321.1 (903.3–1575.3) AU, p = 0.0005). On day 1, the work of breathing was lower in the NIV than the ECCO2R group (4.38 (2.76–7.27) vs. 8.03 (4.8–15.94) J/min, p < 0.0001), minute ventilation was higher (15.54 (13.14–18.48) vs. 12.24 (8.51–13.9) L/min, p < 0.0001) and neural drive was the same (1,163.8 (1,085.5–1,325.5) vs. 1,093.8 (885.7–1,258.7) AU, p = 0.5556). Conclusions The combination of NIV and ECCO2R results in lower work of breathing and improved neuro-ventilatory coupling. NIV fully supports ventilation early whilst ECCO2R improves neuro-ventilatory coupling and work of breathing over time. Trial registration Clinicaltrials.gov; NCT02086084; registered 1 December 2015; https://clinicaltrials.gov/study/NCT02086084?cond=copd&term=ecco2r&rank=4

Association of Blood Glucose Data With Physiological and Nutritional Data From Dietary Surveys and Wearable Devices: Database Analysis

Background Wearable devices can simultaneously collect data on multiple items in real time and are used for disease detection, prediction, diagnosis, and treatment decision-making. Several factors, such as diet and exercise, influence blood glucose levels; however, the relationship between blood glucose and these factors has yet to be evaluated in real practice. Objective This study aims to investigate the association of blood glucose data with various physiological index and nutritional values using wearable devices and dietary survey data from PhysioNet, a public database. Methods Three analytical methods were used. First, the correlation of each physiological index was calculated and examined to determine whether their mean values or SDs affected the mean value or SD of blood glucose. To investigate the impact of each physiological indicator on blood glucose before and after the time of collection of blood glucose data, lag data were collected, and the correlation coefficient between blood glucose and each physiological indicator was calculated for each physiological index. Second, to examine the relationship between postprandial blood glucose rise and fall and physiological and dietary nutritional assessment indices, multiple regression analysis was performed on the relationship between the slope before and after the peak in postprandial glucose over time and physiological and dietary nutritional indices. Finally, as a supplementary analysis to the multiple regression analysis, a 1-way ANOVA was performed to compare the relationship between the upward and downward slopes of blood glucose and the groups above and below the median for each indicator. Results The analysis revealed several indicators of interest: First, the correlation analysis of blood glucose and physiological indices indicated meaningful relationships: acceleration SD (r=–0.190 for lag data at –15-minute values), heart rate SD (r=–0.121 for lag data at –15-minute values), skin temperature SD (r=–0.121), and electrodermal activity SD (r=–0.237) for lag data at –15-minute values. Second, in multiple regression analysis, physiological indices (temperature mean: t=2.52, P=.01; acceleration SD: t=–2.06, P=.04; heart rate_30 SD: t=–2.12, P=.04; electrodermal activity_90 SD: t=1.97, P=.049) and nutritional indices (mean carbohydrate: t=6.53, P&lt;.001; mean dietary fiber: t=–2.51, P=.01; mean sugar: t=–3.72, P&lt;.001) were significant predictors. Finally, the results of the 1-way ANOVA corroborated the findings from the multiple regression analysis. Conclusions Similar results were obtained from the 3 analyses, consistent with previous findings, and the relationship between blood glucose, diet, and physiological indices in the real world was examined. Data sharing facilitates the accessibility of wearable data and enables statistical analyses from various angles. This type of research is expected to be more common in the future.

Elastic Bands During Half-Squats as A Re-Warm-Up Strategy for Youth Soccer Players' Performance.

The study aimed to assess the immediate effects of re-warm-up strategies using half-squats with elastic looped bands on the performance of youth soccer players. A cross-over study design with repeated measures was implemented in field youth male soccer players (n = 20, age 15.7 ± 0.8 years). Following the first 45-min of match play, players were subjected to one of four re-warm-up (Re-w) interventions of equal duration: no Re-w (PAS), half-squat without elastic looped bands (SQ), half-squat with bands placed on the thighs (SQT), and half-squat with bands placed on the lower legs (SQL). These interventions were compared against a control condition (CON). The Re-w protocols were initiated 10-min after half-time, and players' performance was evaluated through vertical and horizontal jump tests, 20-m linear sprint, and T-agility test. Statistical analysis using ANOVA revealed that the SQT and SQL interventions significantly improved (p < 0.001) several performance metrics compared to the PAS and SQ conditions. These improvements were observed in squat jumps, unilateral squat jumps (both dominant and non-dominant legs), countermovement jumps, horizontal jumps, triple horizontal jumps, the 20-m linear sprint, and T-agility performance. In conclusion, SQT and SQL are equally effective to enhance performance as Re-w strategies after the 1st-half of a soccer match. However, the lack of physiological data and 2nd-half assessments suggests the need for further research to confirm the persistence of these effects.

SoutheAsTern eUrope microciRculATION (SATURATION) registry - Design and rationale.

A considerable number of symptomatic patients leave the cardiac catheterization lab without a definitive diagnosis for their symptoms because no epicardial stenoses are found. The significance of disorders of coronary microvasculature and vasomotion as the cause of symptoms and signs of ischemia has only recently been appreciated. Today we have a wide spectrum of invasive coronary physiology tools but little is known about when and how these tools are used in clinical practice. SoutheAsTern eUrope microciRculATION (SATURATION) registry will study the regional practice of patient selection for coronary function testing, indications, non-invasive ischemia testing, medications, procedural aspects of invasive physiology evaluation, and treatment changes after testing. The registry is expected to include 1600 patients in participating centers in Southeastern Europe from 2024 to 2029, using the thermodilution technique for evaluation of microcirculation. Major adverse cardiovascular events as well as patient-centered outcomes such as burden of angina and quality of life using Seattle Angina Questionnaire (SAQ) and EQ-5D-5L will be recorded. The study will include patients with different stages of coronary artery disease (presence of disease or degree of stenosis) to elucidate the effect of coronary microcirculation on the outcomes in this broad group. The registry will provide information regarding the current practice of invasive coronary physiology assessment in populations at high cardiovascular risk in Southeastern Europe. This could lead to a better understanding of coronary microvascular dysfunction and its relationship to various degrees of coronary atherosclerosis together with potential interventions that can be beneficial.

Ischemia with Non-Obstructive Coronary Arteries

Many patients with angina or evidence of myocardial ischemia on noninvasive tests have no obstructive coronary artery disease. Ischemia with non-obstructive coronary arteries (INOCA) has been underrecognized despite its association with poor quality of life and effect on cardiovascular events. Two major mechanisms, coronary microvascular dysfunction (CMD) and coronary vasospasm, are keys to INOCA pathophysiology. Although noninvasive tests, such as stress echocardiography, cardiac positron emission tomography, and cardiac magnetic resonance imaging, offer evidence of CMD, the gold standard for diagnosing INOCA is coronary angiography with a comprehensive physiological assessment and provocation test of coronary vasospasm. Here, we provide the etiology and pathophysiology of INOCA and guide for the diagnostic approach and treatment of INOCA.

Combined effects of fluoroquinolone antibiotic enrofloxacin and rising sea temperatures on the health of the Mediterranean mussel (Mytilus galloprovincialis): exploring physiological, biochemical, and energetic balance dynamics.

Human activity exposes organisms in marine ecosystems to numerous stressors, including rising seawater temperatures and antibiotic contamination. The present study investigated the impacts of environmentally relevant concentrations of the fluoroquinolone (FQ) antibiotic enrofloxacin (ENR), specifically 5 and 500 ng/L, in Mytilus galloprovincialis under ambient (20 °C) and predicted warming (25 °C) conditions after 14 days of exposure, followed by a 14-day recovery period in the absence of ENR. The chemical analyses revealed significant variability in bioaccumulation in mussel tissues. Physiological assessments showed decreased respiration and filtration rates post-exposure, with temperature-dependent recovery dynamics. Biochemical parameters indicated an increased metabolic capacity and energy reserves at higher temperatures, with a significant increase in energy expenditure. Notably, ENR induced significant DNA single-strand breaks in mussel gills and digestive glands, with temperature influencing DNA repair mechanisms. The combination of ENR and elevated temperatures exhibited additive or even synergistic effects on certain physiological and biochemical parameters, indicating a higher risk when these stressors act together. The Indipendent Action model (IA) results highlighted that the majority of observed effects in combined stressors were consistent with predicted values, with notable synergistic interactions in energy reserves and antagonistic responses in metabolic and physiological functions. These findings suggest that both stressors, acting alone and especially in combination, may pose a risk to marine bivalves such as mussels. Further research is needed to assess the impacts of FQs and ocean warming on ecosystem stability and non-target organisms.

Developing drought and heat-resistant grapevine cultivars through marker-assisted breeding

Climate change poses significant challenges to viticulture, particularly through increased drought and heat stress. This study integrates physiological, biochemical, genomic, and field performance assessments to identify traits and genetic markers associated with stress tolerance in five grapevine cultivars: Cabernet Sauvignon, Chardonnay, Syrah, Merlot, and Riesling. Genomic analysis revealed specific SNP markers on chromosomes 4 and 8, linked to water-use efficiency (WUE) and proline accumulation, crucial for osmotic balance under drought conditions. Physiological assessments showed that Cabernet Sauvignon and Merlot maintained high relative water content and low stomatal conductance, reducing water loss. Biochemical analysis indicated that Chardonnay and Syrah had elevated heat shock protein (HSP) expression and low malondialdehyde (MDA) levels, supporting cellular stability under heat. Field trials further validated these traits, with Cabernet Sauvignon and Chardonnay demonstrating yield stability and high sugar content despite stress. This research underscores the potential of marker-assisted breeding to develop climate-resilient grapevine cultivars, offering practical insights for sustainable viticulture in the face of global climate shifts.

A new 3D vision-based leaf rolling index (LRI) and its application as a stable indicator of cotton drought stress

The leaf rolling index (LRI) is a phenotype with significant physiological implications under drought stress. However, research on the quantification of the cotton LRI is lacking, limiting its application in drought diagnosis, irrigation guidance, and physiological assessments. This study conducted a 3D reconstruction of cotton using Structure from Motion (SFM) and Multi-View Stereo (MVS). Algorithms for leaf point cloud preprocessing and phenotype extraction were developed using the PCL point cloud library and integrated into software to calculate the leaf area and perimeter. The LRI was quantified in 3D space based on the point cloud area ratio. On this basis, we analyze the relationships between LRI and leaf physiological indicators such as leaf water potential (LWP), relative water content (RWC), stomatal conductance (gs), and electron transport rate (ETR) at the seedling and flowering stages. The results indicate that the cotton LRI provides a stable indicator of drought stress, which is mainly reflected in the stable correlation between the LRI and water physiological parameters (LWP, and RWC), with coefficients of determination (R²) exceeding 0.70. Furthermore, the correlation between the LRI and the ETR suggests that the LRI could be used to assess photosynthetic efficiency under drought stress. This study demonstrates that LRI based on 3D vision in cotton may serve as a reliable morphological indicator for indicating drought stress and evaluating photosynthetic efficiency.

Integrating morphology, physiology, and computer simulation to reveal the toxicity mechanism of eco-friendly rosin-based pesticides

To mitigate the impact of traditional chemical pesticides on environment, and achieve sustainable crop protection, 24 eco-friendly rosin-based sulfonamide derivatives were synthesized and developed. The in vitro activity assessment showed that compound 4X (Co. 4X) exhibited excellent fungicidal activity against V. mali (EC50 = 1.106 μg/mL), marginally surpassing the positive control carbendazim (EC50 = 1.353 μg/mL). In vivo investigations suggested that Co. 4X exhibited moderate efficacy in mitigating V. mali infection in both apple trees and apples. Physiological assessments revealed that Co. 4X induced severe ultrastructural damage to the mycelium, heightened cell membrane permeability, and inhibited SDH protein activity. Subsequent biosafety evaluations affirmed the environment-friendly of Co. 4X on Zebrafish (LC50(96h) = 25.176 μg/mL). Toxicological research revealed that Co. 4X caused damage to the cells of Zebrafish gills, liver, and intestines, resulting in impaired respiratory, detoxification, digestion, and absorption functions of Zebrafish. In summary, the findings of this study contribute to a deeper understanding of the toxicity mechanisms of novel pesticides, decreasing environmental risks caused by traditional chemical pesticides, and improving the effective management of novel pesticide applications.

VR and Physiological Assessment Technologies Applied on the Touring Perception of Chinese Classical Gardens

This paper reviews on the research status and new progress in the field of Chinese classical gardens by the application of new technologies including virtual reality and physiological measurements. Firstly, it introduces the background and significance of current research in the field of spatial creation in Chinese classical gardens. Then, this paper combs relevant literature on the application of VR and physiological research methods on landscape and architectural studies in recent years. Finally, the possibilities of applying physiological data and virtual reality in the exploration of the spatial perception of Chinese classical gardens is discussed. The results could provide inspiration sources and technical references for the empirical studies of future landscape research on Chinese classical gardens.

Integrated Assessment of Coronary Physiology Based on Coronary Angiography in Heart Transplant Patients.

Early detection of cardiac allograft vasculopathy after heart transplant (HTx) with invasive coronary angiography is challenging. The study aimed to determine if computational techniques able to assess epicardial lesions, by means of Murray's law-based quantitative flow ratio (μFR), and microvascular physiology, by means of angiography microvascular resistance (AMR), enhance risk stratification in HTx patients with nonsignificant coronary artery disease. The cohort consisted of 86 consecutive HTx patients (200 epicardial vessels) with stenosis < 50% at baseline. μFR ≤ 0.80 indicated coronary ischemia, while AMR ≥ 2.5 suggested microvascular dysfunction. Clinical events were assessed over a median follow-up of 43 months, focusing on the relationship between μFR and target vessel failure (TVF), and between AMR and heart failure (HF) hospitalizations. At baseline, mean μFR was 0.94 ± 0.08, with eight vessels (4.0%) disclosing flow-limiting lesions, while AMR was 2.4 ± 0.7, with 80 vessels/40 patients (40.0%/46.5%) having microvascular dysfunction. TVF-related segments were associated with lower mean μFR values (0.89 ± 0.14 vs. 0.95 ± 0.05; p < 0.007) compared TVF-free segments. At the receiver operating characteristic curve a μFR ≤ 0.93 demonstrated an area under the curve of 0.632 (95% CI: 0.562-0.699) in predicting TVF occurrence, showing an accuracy of 76.0%, a sensitivity of 46.9%, a specificity of 81.6%, a negative predictive value of 89.0%, and a positive predictive value of 32.6%. μFR ≤ 0.93 showed a significant interaction with TVF occurrence at 43 months (32.6% vs. 11.0%; HR: 2.96; 95% CI: 1.26-6.96; p = 0.013). Microvascular dysfunction showed a significant interaction with HF hospitalizations occurence (AMR: 2.8 ± 4.4 vs. 2.4 ± 4.5; p = 0.001; CMD: 27.5% vs. 4.3%; HR: 7.36; 95% CI: 2.45-22.07; p = 0.002). Angiography-derived epicardial and microvascular physiology computation may improve risk stratification of heart transplanted patients.

Coronary microvascular function and atherosclerotic plaque burden in ischaemia and no obstructive coronary arteries: a secondary analysis of the CorMicA trial

BackgroundThe relationship between atherosclerosis and endotypes of myocardial ischaemia with no obstructive coronary artery disease (INOCA) is unclear. We investigated potential associations between cumulative atherosclerotic plaque burden quantified using the...

Lycium barbarum Polysaccharide Alleviates Amyloid‐β‐Induced Toxicity in the Caenorhabditis elegans Model

ABSTRACTAlzheimer's disease (AD) poses a significant global health challenge, primarily characterized by the aggregation of β‐amyloid (Aβ) peptides and associated oxidative stress. Given the lack of effective AD drugs, we investigated the effects of Lycium barbarum polysaccharide (LBP), a water‐soluble polysaccharide from goji berries, on Aβ scavenging, aggregation, and Aβ‐induced toxicity using the transgenic AD nematode. LBP treatment delayed paralysis, mitigated Aβ‐induced chemotaxis deficits, and reduced Aβ1–42 deposition and oligomer formation in AD nematodes. Furthermore, LBP supplementation alleviated Aβ‐induced oxidative stress and improved oxidative stress resistance through the insulin/insulin growth factor 1 (IGF‐1) signaling (IIS) pathway. Evaluation of the Aβ clearance pathway revealed that LBP attenuated Aβ toxicity by increasing proteasome activity rather than lysosomal levels. Basic physiological assessments further indicated that LBP was non‐toxic in vivo and promoted nematode health. Our findings suggest that LBP ameliorates AD‐like symptoms in nematodes by activating the IIS pathway to reduce oxidative stress and enhancing proteasomal activity to clear Aβ aggregates, providing a new theoretical basis for considering LBP as a promising therapeutic drug for AD and related oxidative stress complications.

Redefining Molecular Probes for Monitoring Subcellular Environment: A Perspective.

The development of small-molecule fluorescent probes has revolutionized the monitoring of in vivo physicochemical parameters, offering unprecedented insights into biological processes. In this perspective, we critically examine recent advances and trends in the design and application of fluorescent probes for real-time in vivo monitoring of subcellular environments. Traditional concepts such as membrane potential, microviscosity, and micropolarity have been superseded by more biologically relevant parameters like membrane voltage, tension, and hydration, enhancing the accuracy of physiological assessments. This redefinition not only presents an evolved concept with broader applications in monitoring subcellular dynamics but also addresses the unmet needs of subcellular biology more effectively. We also highlight the limitations of commonly used probes in providing specific information about the redox environment, noting their nonspecificity to oxidants and the influence of various chemical interactions. These probes typically rely on free radical mechanisms and require metal catalysts to react with hydrogen peroxide. They include naphthalimide, fluorescein, BODIPY, rhodamine, cyanine cores to cover the UV-vis-near-infrared window. The motif of this perspective is to provide critical insights into trending fluorescent-based systems employed in real-time or in vivo physicochemical-responsive monitoring, thus aiming to inform and inspire further research in creating robust and efficient fluorescent probes for comprehensive in vivo monitoring applications.

Motivational dysregulation with melanocortin 4 receptor haploinsufficiency

Abstract Obesity, by any standard, is a global health crisis. Both genetic and dietary contributions to the development and maintenance of obesity were integral factors of our experimental design. As mutations of the melanocortin 4 receptors (MC4R) are the leading monogenetic cause of obesity, MC4R haploinsufficient rats were fed a range of dietary fat (0–12 %) in a longitudinal design. Physiological and motivational assessments were performed using a locomotor task, a 5-choice sucrose preference task, an operant task with fixed and progressive ratios, as well as a distraction operant task. Dendritic spine morphology of medium spiny neurons (MSNs) of the nucleus accumbens (NAc), cells with ample D1 and D2 receptors, was also assessed. The percentage of lipid deposits in the liver of each rat was also analyzed using the Area Fraction Fractionator probe for stereological measurements. MC4R haploinsufficiency resulted in a phenotypic resemblance for adult-onset obesity that was exacerbated by the consumption of a high-fat diet. Results from the operant tasks indicate that motivational deficits due to MC4R haploinsufficiency were apparent prior to the onset of obesity and exacerbated by dietary fat consumption after obesity was well established. Moreover, MSN morphology shifted to longer spines with smaller head diameters for the MC4R+/− animals under the high-fat diet, suggesting a potential mechanism for the dysregulation of motivation to work for food. Increasing our knowledge of the neural circuitry/mechanisms responsible for the rewarding properties of food has significant implications for understanding energy balance and the development of obesity.

Isolating the direct effects of growth hormone on lifespan and metabolism in mice.

Prior studies have shown that interrupting the growth hormone/insulin-like growth factor-I (GH/IGF-I) signaling axis extends laboratory mouse lifespan, but confounding effects of additional gene or hormone deficiencies that exist in commonly used models of GH/IGF-I interruption obscure the specific effect of GH on longevity. We address this issue by using mice with a specific knockout of the GH gene and show that both males and females on a mixed genetic background display extended lifespans resulting from GH deficiency. Our physiological assessment of these mice revealed that in addition to weighing significantly less and displaying significantly greater body fat (as a percentage of body weight), GH deficient mice display significant impairments in glucose metabolism and preferential fat utilization. These data provide strong evidence that GH deficiency is directly responsible for the altered nutrient utilization and extended lifespan that is commonly observed in mouse models of GH/IGF-I interruption.

Physiological and hygienic assessment of the organization of specialized training for high school students

Introduction. The educational activities in children and adolescents are associated with significant potential health risks, especially during the preparation period for the unified state exam. In this regard, there is a need to optimize the management of educational activities to reduce the physiological cost of the educational process. The purpose of the study is a physiological and hygienic assessment of the management of specialized training of high school students and its impact on the functional state of their body. Materials and methods. The object of the study was two hundred fifty eight students of the 11th grade of the medical pre-university. A study was conducted on the specifics of the management of pre-university education, as well as a hygienic assessment of the curriculum. To assess the impact of the educational process on the functional state of the body in high school students, an assessment of the method of proof-reading tests was carried out by mental performance. Also there was performed a study of the psycho-emotional state of the body using the Izard method and the functional state of the body using the method for studying well-being, activity, and mood. The obtained results were processed using descriptive statistics methods. Results. The similarity of the management of classes with the university form of education is noted. The evaluation of the schedule showed a decrease in the level of academic load over the course of the academic year, as well as the irrationality of scheduling from the point of view of age physiology. During the academic year, positive trend in indicators of mental performance and functional state of the body in students was noted. A high prevalence of pronounced and severe degrees of anxiety-depressive (33.9%) and adverse (29.0%) emotions among high school students was revealed. The relationship between the severity of adverse and anxiety-depressive emotions and the subjective assessment of the state of the body by students is noted. Limitations. The study was conducted in one educational institution, which is a pre-university medical university, which had an impact on the representativeness of the sample. Conclusion. The conducted research shows the system of management of pre-university education allows students successful and effective engaging in educational activities, which is reflected in the positive trend in indicators characterizing the functional state of the body in high school students. Measures to prevent the prevalence of adverse and anxiety-depressive emotions among students are proposed.

SiRNA targeting PARP-1 alleviates diabetic peripheral neuropathy in a streptozotocin-induced rat model

Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes mellitus, affecting nearly 50% of diabetic patients and leading to chronic pain, numbness and progressive sensory and motor function loss. This study investigates the potential of siRNA-mediated silencing of poly(ADP-ribose) polymerase 1 (PARP1) to alleviate DPN in a rat model. PARP1 overactivation, driven by hyperglycaemia-induced oxidative stress, exacerbates neuronal damage in DPN. Using chitosan nanoparticles (ChNPs) to deliver PARP1-targeting siRNA intrathecally in diabetic rats induced with streptozotocin (STZ) 55 mg/kg intraperitoneally, we conducted behavioural and physiological assessments, including Sciatic Functional Index (SFI), motor nerve conduction velocity (MNCV), grip strength and pain sensitivity tests, alongside qRT-PCR analyses, to evaluate therapeutic outcomes. Our findings indicate statistically significant improvements, with siRNA ChNPs-mediated PARP1 silencing alleviating neuropathic symptoms in DPN rats (p < .001 for SFI and MNCV improvements). Biochemical analyses revealed reductions in oxidative stress markers, such as MDA, and increased antioxidant levels, including GSH, CAT and SOD (p < .001). Pro-inflammatory cytokines and apoptotic markers, including NF-κB, IL6, IL1β, TNFa, TGF-β, CAS3, CAS9, BAK and BAX, also showed significant reductions (p < .01), confirming the neuroprotective effects of PARP1 inhibition. These results highlight the potential of siRNA-based therapies targeting PARP1 as a promising therapeutic approach for DPN, paving the way for future research with clinical applications.

Development of a protocol for whole-lung in vivo lung perfusion-assisted photodynamic therapy using a porcine model.

Standard treatments for isolated lung metastases remain a clinical challenge. In vivo lung perfusion technique provides flexibility to overcome the limitations of photodynamic therapy (PDT) by replacing the blood with acellular perfusate, allowing greater light penetration. Using Monte Carlo-based simulations, we will evaluate the abilities of a light delivery system to irradiate the lung homogenously. Afterward, we aim to demonstrate the feasibility and safety profile of a whole-lung perfusion-assisted PDT protocol using 5-ALA and Chlorin e6. A porcine model of a simplified lung perfusion procedure was used. PDT was performed at 630 or 660nm with 5-ALA or Chlorin e6, respectively. Light fluence rate measurements and computed tomography (CT) scan segmentations were used to create in silico models of light propagation. Physiologic, gross, CT, and histological assessment of lung toxicity was performed 72h post-PDT. Dose-volume histograms showed homogeneity of light intensity throughout the lung. Predicted and measured fluence rates showed strong reliability. The photodynamic threshold of 5-ALA was , whereas Chlorin e6 showed negligible uptake in lung tissue. We lay the groundwork for personalized preoperative in silico dosimetry planning to achieve desired treatment volumes within the therapeutic range. Chlorin e6 demonstrated the greatest therapeutic potential, with a minimal uptake in healthy lung tissues.

Diagnostic Performance of Quantitative Flow Ratio for the Assessment of Non-Culprit Lesions in Myocardial Infarction (QFR-OUTSMART): Systematic Review and Meta-Analysis.

Quantitative flow ratio (QFR) analysis is a simple and non-invasive coronary physiological assessment method with evidence for evaluating stable coronary artery disease with correlation to fractional flow reserve (FFR). However, there is no evidence to recommend its use in non-culprit lesions (NCLs) in myocardial infarction (MI). We performed a systematic review and meta-analysis using the PRISMA and PROSPERO statements. The study's primary objective was to assess the diagnostic accuracy of QFR in identifying functionally significant NCLs after MI based on invasive FFR and non-hyperemic pressure ratios as references. We obtained values of the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We performed a leave-one-out sensitivity analysis for each study's impact on the overall effect. We included eight studies, with 713 patients and 920 vessels evaluated with QFR. The overall AUC was 0.941 (I2 = 0.559, p < 0.002), with a sensitivity of 87.3%, a specificity of 89.4%, a PPV of 86.6%, and an NPV of 90.1%. Compared to FFR, we found an AUC of 0.957 (I2 = 0.331, p < 0.194), a sensitivity of 89.6%, a specificity of 89.8%, a PPV of 88.3%, and an NPV of 91%. The sensitivity analysis showed a similar diagnostic performance in both studies. QFR is effective in analyzing NCLs with a significant diagnostic yield compared to FFR, with an excellent AUC in MI patients. Performing prospective multicenter studies to characterize this population and reproduce our results is essential.