Functional Variables Research Articles

The Effect of special exercises on some of the functional variables and offensive skills of the players of the National Youth Squash

The importance of research is through the knowledge of the role of special exercises and the preparation of a set of special exercises according to the correct scientific bases in sports training and the adoption of modern methods and methods and knowledge of the impact of some functional variables and offensive skills of the national team of youth squash game, through the researcher's experience and record his observations and diagnosis about these games found The level of special physical abilities, including the ability to endure the force and speed in the young players in most games, which involve the decline of the level of physical performance and skill in the last half of the squash games, Due to the decrease in the concentration of lactic acid and some other functional variables to be studied, the most important objectives: To identify the effect of special exercises in some functional variables of the players of the national team for youth Squash. The members of the research sample to recognize the impact of special exercises in some of the offensive skills of the national youth team Balasquash individuals sample research. The researcher used the experimental method in one of its basic determinants (by identifying the one group with the pre-test and the post-test). The sample was chosen by the intentional method and included (6) squash players aged (19-17) years. The most important conclusions: The development of the capacity resulting from the special exercises came in line with what has been implemented to the level of the members of the research sample, which was reflected clearly on the skill performance. The repetition of exercises within the training modules that have been applied positively affected the development of the muscles of the arms and legs together and reflected in Directly on the development of functional capabilities. Special exercises have a positive effect in raising the skill level of some offensive skills in squash.

Evaluation of short-term mortality in patients with Medicare undergoing endovascular interventions for chronic limb-threatening ischemia.

Patients with chronic limb-threatening ischemia (CLTI) have high mortality rates after revascularization. Risk stratification for short-term outcomes is challenging. We aimed to develop machine-learning models to rank predictive variables for 30-day and 90-day all-cause mortality after peripheral vascular intervention (PVI). Patients undergoing PVI for CLTI in the Medicare-linked Vascular Quality Initiative were included. Sixty-six preprocedural variables were included. Random survival forest (RSF) models were constructed for 30-day and 90-day all-cause mortality in the training sample and evaluated in the testing sample. Predictive variables were ranked based on the frequency that they caused branch splitting nearest the root node by importance-weighted relative importance plots. Model performance was assessed by the Brier score, continuous ranked probability score, out-of-bag error rate, and Harrell's C-index. A total of 10,114 patients were included. The crude mortality rate was 4.4% at 30 days and 10.6% at 90 days. RSF models commonly identified stage 5 chronic kidney disease (CKD), dementia, congestive heart failure (CHF), age, urgent procedures, and need for assisted care as the most predictive variables. For both models, eight of the top 10 variables were either medical comorbidities or functional status variables. Models showed good discrimination (C-statistic 0.72 and 0.73) and calibration (Brier score 0.03 and 0.10). RSF models for 30-day and 90-day all-cause mortality commonly identified CKD, dementia, CHF, need for assisted care at home, urgent procedures, and age as the most predictive variables as critical factors in CLTI. Results may help guide individualized risk-benefit treatment conversations regarding PVI.

Technical evaluation and standardization of the human thyroid microtissue assay.

The success and sustainability of U.S. EPA efforts to reduce, refine, and replace in vivo animal testing depends on the ability to translate toxicokinetic and toxicodynamic data from in vitro and in silico new approach methods (NAMs) to human-relevant exposures and health outcomes. Organotypic culture models employing primary human cells enable consideration of human health effects and inter-individual variability but present significant challenges for test method standardization, transferability, and validation. Increasing confidence in the information provided by these in vitro NAMs requires setting appropriate performance standards and benchmarks, defined by the context of use, to consider human biology and mechanistic relevance without animal data. The human thyroid microtissue (hTMT) assay utilizes primary human thyrocytes to reproduce structural and functional features of the thyroid gland that enable testing for potential thyroid-disrupting chemicals. As a variable-donor assay platform, conventional principles for assay performance standardization need to be balanced with the ability to predict a range of human responses. The objectives of this study were to (1) define the technical parameters for optimal donor procurement, primary thyrocyte qualification, and performance in the hTMT assay, and (2) set benchmark ranges for reference chemical responses. Thyrocytes derived from a cohort of 32 demographically diverse euthyroid donors were characterized across a battery of endpoints to evaluate morphological and functional variability. Reference chemical responses were profiled to evaluate the range and chemical-specific variability of donor-dependent effects within the cohort. The data-informed minimum acceptance criteria for donor qualification and set benchmark parameters for method transfer proficiency testing and validation of assay performance.

Some functional, biochemical and skill variables resulting from the ef-fect of special exercises for advanced basketball players


 The importance of a research on the practical application of this method has emerged because this training method is one of the modern methods used in sports training that works to develop some functional, biochemical and skill abilities faster and in a shorter time than other traditional training methods. In the last quarter of the match (the fourth quarter), the researchers noticed a weakness in skills through a decrease in concentration among the players in the last minutes of the match. This problem appeared in all players through a decline in the level of performance result-ing from fatigue, which affects functional, biochemical and skill variables. This is a result of the lack of concentration in shooting in the last quarter of the match, and this is what most coaches of Iraqi Premier League basketball clubs suffer from, which made the researchers pay attention to this problem and find solutions to it by applying special exercises and knowing their impact on the functional, biochemical and skill abilities of advanced basketball players, and aims search: To prepare spe-cial exercises for some functional, biochemical and skill variables for advanced basketball players. And to identify the effect of special exercises on some functional, biochemical and skill variables for advanced basketball players. The researchers adopted the experimental method as it was the most appropriate to the nature of the problem to be studied using a two-group method for the experimental and control groups. The research population was identified as (12) Premier League basketball players for the 2022-2023 sports season, and the Tigris University Club was chosen intentionally to be the research sample. The club consists of (12) players, and by dividing the sample of research individuals into two groups (experimental and con-trolled). The distribution was (6) players for each group. The researcher used ap-propriate tests for the purpose of extracting variables, and the results were pro-cessed using appropriate statistical methods. The researchers came to the following conclusions:1- The researchers’ use of exercises had a positive impact during the training units on the players, which contributed to the development of functional, biochemical and skill variables among the basketball players of the research sample in the pre- and post-tests.In light of the conclusions reached by the researchers, the researchers can recom-mend the following:1- Using scientific principles when developing and preparing exercises in terms of intensity, volume, and comfort, because of its positive impact on developing the functional, biochemical, and skill variables in basketball for the experimental group.
 

Movement efficiency in survivors of childhood acute lymphoblastic leukemia: a report from the St. Jude lifetime cohort study.

Movement efficiency, a measure of neuromuscular biomechanics, may be modified by physical activity. We aimed to assess the risk of and risk factors for low movement efficiency in survivors of childhood acute lymphoblastic leukemia (ALL). Participants underwent an assessment of activity energy expenditure (AEE) with actigraphy, and the gold standard doubly labeled water, where the differences between elimination rates of oxygen and hydrogen from body water are evaluated over a week. Movement efficiency was assessed using the raw residuals of a linear regression between AEEs from accelerometers and doubly labeled water. Elastic-net logistic regressions were used to identify demographic, treatment, and functional variables associated with movement efficiency. The study cohort included 256 non-cancer controls and 302 ALL survivors (48% female), categorized as efficient (N = 24), normal (N = 245), or inefficient (N = 33) based on their movement efficiency. There was no difference in the odds for poor movement efficiency between survivors (n = 33, 10.9%) compared to controls (n = 23, 9.0%, odds ratio [OR]: 1.19, 95% confidence interval [CI]: 0.67, 2.10; p = 0.55). In survivors, neuropathy was associated with a higher risk of being inefficient compared to efficient (OR 4.30, 95% CI 1.03-17.96), while obesity (≥ 30kg/m2) had a protective association (OR 0.18, 95% CI 0.04-0.87). Neuropathy was associated with a higher risk of poor movement efficiency in survivors of childhood ALL. These results further highlight impairments associated with treatment-induced neuropathy in survivors of childhood ALL.

Cognitive outcomes in patients with essential tremor treated with deep brain stimulation: a systematic review.

Essential tremor (ET) is a common neurological disease. Deep brain stimulation (DBS) to the thalamic ventral intermediate nucleus (VIM) or the adjacent structures, such as caudal zona incerta/ posterior subthalamic area (cZi/PSA), can be effective in treating medication refractory tremor. However, it is not clear whether DBS can cause cognitive changes, in which domain, and to what extent if so. We systematically searched PubMed and the Web of Science for available publications reporting on cognitive outcomes in patients with ET who underwent DBS following the PICO (population, intervention, comparators, and outcomes) concept. The PRISMA guideline for systematic reviews was applied. Twenty relevant articles were finally identified and included for review, thirteen of which were prospective (one also randomized) studies and seven were retrospective. Cognitive outcomes included attention, memory, executive function, language, visuospatial function, and mood-related variables. VIM and cZi/PSA DBS were generally well tolerated, although verbal fluency and language production were affected in some patients. Additionally, left-sided VIM DBS was associated with negative effects on verbal abstraction, word recall, and verbal memory performance in some patients. Significant cognitive decline after VIM or cZi/PSA DBS in ET patients appears to be rare. Future prospective randomized controlled trials are needed to meticulously study the effect of the location, laterality, and stimulation parameters of the active contacts on cognitive outcomes while considering possible medication change post-DBS, timing, standard neuropsychological battery, practice effects, the timing of assessment, and effect size as potential confounders.

Circadian rhythm and variability of large and small airway spirometric variables in healthy individuals.

To assess the diurnal rhythm and variability of lung function in healthy individuals, encompassing both large and small airways. A prospective study enrolled 35 healthy adults without a history of smoking. Initial spirometry and a bronchodilation test were performed using the Jaeger spirometer, followed by a seven-day continuous home monitoring using the GOSPT2000. We evaluated repeatability using the intraclass correlation coefficient and agreement through linear regression and Bland-Altman analyses. Circadian rhythm and variability in spirometric measurements were analyzed using the coefficient of variation (CV) and daily variation rate. The GOSPT2000 demonstrated strong repeatability and high agreement with the Jaeger spirometer. Notable findings included a decrease in nocturnal forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV3 by 44, 59, and 53 mL, respectively. In contrast, peak expiratory flow at noon showed an increase of 0.143L/min. Small-airway variables, including forced expiratory flow at 50% and 75% of the FVC and maximum midexpiratory flow, showed no significant diurnal variation. The nocturnal CV for large-airway variables was ≤ 4%, while for small-airway variables, it was ≤ 11.89%. This study has established a spectrum of variability for both large and small airways in healthy populations. The variability of small-airway variables is higher than that of large-airway variables. The investigation into the diurnal rhythms and variability characteristics of both large and small airway variables in the healthy population can serve as a foundation for diagnosing asthma or assessing the efficacy of asthma treatments.

Assessment of Right Ventricular Function by Strain Imaging in Patients Presenting with Acute Myocardial Infarction: An Original Research

ABSTRACT Objective: This study sought to determine the relationship between right ventricular (RV) function and clinical variables and prognosis in individuals with acute myocardial infarction (AMI) utilizing strain imaging. Materials and Methods: A prospective observational research involving 150 patients who had been admitted with AMI was carried out. Utilizing two-dimensional speckle-tracking strain imaging, RV function was assessed. Age, sex, risk factors, and comorbidities were recorded as clinical parameters. A 12-month follow-up was conducted to assess major adverse cardiovascular events (MACE). Results: 65% of the study’s participants were men, with a mean age of 58.2 years. When compared to a healthy control group, individuals with AMI had significantly lower RV longitudinal strain (RVLS) (P 0.001). RVLS and left ventricular ejection fraction had a statistically significant connection (r = 0.642, P 0.001). Patients with compromised RVLS had a greater rate of MACE over the follow-up period compared to those with maintained RV function (P = 0.014). Conclusion: In conclusion, strain imaging offers useful information for evaluating RV function in patients with AMI. Reduced left ventricular performance and a higher likelihood of unfavorable clinical outcomes are linked to impaired RVLS. Utilizing strain imaging to detect RV dysfunction early can help direct treatment plans and enhance patient outcomes.

Initial experience with thulium fiber laser for prostate enucleation: Analysis of the intraoperative and short-term outcomes in a prospective, multicenter cohort

IntroductionHolmium laser enucleation of the prostate has rapidly become the gold standard for the surgical treatment of benign prostate hyperplasia, although thulium fiber laser (TFL) has also been postulated as an effective and safe alternative for prostate enucleation. The aim of this study is to describe our initial experience with the TFL for endoscopic enucleation of the prostate. Material and methodsAll patients proposed to TFL prostate enucleation were included in the analysis, regardless their prostate volume, catheter status and severity of symptoms, in 3 centers. Preoperative characteristics, intraoperative times and functional 3-months follow-up variables were collected, along with complications. ResultsFifty-six patients were available, with a mean age of 68.7 years. Enucleation and morcellation efficiencies were 2.04 and 7.47 g/min, respectively. Median hospital stay was one day. Comparable functional data, pre and 3-month post-surgery was: mean prostate volume 88.9 vs 21.3 g, maximum urinary flow 13.2 vs 27.3 ml/s, post-void residual volume 149 vs 7.8 ml, prostatic specific antigen level 11.2 vs 1 ng/ml, and International Prostate Symptom Score 20.75 vs 3.96. Fourteen out of 56 (25%) patients presented with complications grade ≤2, according to the Clavien-Dindo classification. DiscussionWith wider evidence for other urological indications, very recent evidence about the suitability of TFL for prostate enucleation has arisen, since the first case described in 2021. Our results seem to back up these previous successful experiences as long as we obtained good intraoperative and short term follow-up functional results. However, there is still a need of longer follow-up data. ConclusionsTFL represents a novel technology for prostate enucleation, with a good intraoperative and short follow-up functional results, and a safety profile similar to the observed for those techniques that have been wider used for this indication. Further studies with longer follow-up periods and comparative with these other techniques are necessary.

Abstract 51: Impact of Cerebral Autoregulation on the Relationship Between Blood Pressure Variability and Functional Outcome Following Endovascular Thrombectomy

Background: Both increased blood pressure (BP) variability and impaired autoregulation have been linked to worse outcome after endovascular thrombectomy (EVT). This study examined the combined effect of these variables on the risk of poor outcome in patients with large-vessel occlusion (LVO) stroke. Methods: Autoregulation was continuously measured for up to 24 hours after EVT and quantified as a moving correlation coefficient between arterial BP and the near-infrared spectroscopy-derived cerebral oxygen saturation. Systolic BP variability was assessed using the standard deviation of the mean. Values were averaged for the entire recording period and dichotomized at the lowest tertile for both variables. Functional outcome was assessed using the modified Rankin scale (mRS) at 90 days and dichotomized into good (mRS 0-2) and poor outcome (mRS 3-6). Results: We included 195 patients (mean age 70 + 16, 45% female, mean NIHSS 14, mean monitoring time 15 + 7 hours). After adjusting for age, NIHSS, ASPECTS, and TICI score, patients with low BP variability and intact autoregulation were significantly more likely to achieve a good outcome than those with high BP variability and impaired autoregulation (OR 3.7, 95% CI 1.2-12.1, p=0.028, Figure 1A). We found an interaction between BP variability and autoregulation (p=0.067). Patients with high BP variability showed a gradual decrease in the probability of a good outcome with worsening autoregulation. However, for patients with low BPV, autoregulation had minimal impact. (Figure 1B). No significant correlation was seen between autoregulatory function and BP variability (r=0.07, p=0.33). Conclusions: For LVO stroke patients with high BP variability after EVT, worse 90-day functional outcome may be exacerbated by impaired autoregulation. These results suggest that autoregulatory status should be considered in the management of BP after EVT to identify high-risk patients and develop individualized treatment strategies.

Effects of microhabitat features on the intraspecific variability of the distribution and functional traits in a highest elevational distributed lizard.

Exploring the microhabitat determinants of organisms distribution and functional traits differences can help us better understand the importance of intraspecific variations in ecological niches. Investigations on animals functional niche primarily focused on differences among species and tended to neglect the potential variability within species, despite the fact that the ecological and evolutionary importance of intraspecific variations was widely recognized. In this study, we examined the influence of microhabitat features on the intraspecific variability of the distribution and functional traits of a highest elevational distributed lizard species Phrynocephalus erythrurus. To do so, field work was conducted between July and August, 2020 and August and September, 2021 in Namtso watershed in central Xizang, China. Specifically, 11 transects were sampled for P. erythrurus individuals, which were measured for a set of 10 morphological traits. Moreover, 11 microhabitat variables that potentially affect the distribution of lizards were also measured for each transect. Our results indicated that juveniles, males, and females exhibited different functional traits, allowing them to occupy distinct functional space. The distribution of juveniles, males, and females was determined by different microhabitat variables such as illuminance and air temperature. More importantly, these variables also determined the intraspecific functional traits variability in this lizard species. All of these results supported previous claims that intraspecific traits variation should be incorporated into functional ecological studies, and diverse microhabitat features should be conserved to maintain high intraspecific diversity. Future studies can focus on the food analysis to explore the linkage between functional traits and resources utilization within animal populations.

Decreased temporal variabilities of functional connectivities in insula and lingual gyrus are associated with better early treatment response in patients with panic disorder.

Panic disorder is a common disabling condition with limited biomarkers. We aimed to explore the diagnostic and treatment response prediction value of functional temporal variability in people with panic disorder. Patients with panic disorder and healthy controls received resting-state functional magnetic resonance imaging scans and assessments. After 2 weeks of treatment, the patients with panic disorder were divided into remitted (RPD; n = 39) or nonremitted (NRPD; n = 43) subgroups. Baseline temporal variability was analyzed between the panic disorder and control groups as well as between RPD and NRPD subgroups. Our sample included 82 patients with panic disorder (39 RPD, 43 NRPD) and 105 controls. The panic disorder group showed decreased temporal variability in the left posterior cingulate gyrus (PCG), right lingual gyrus, right fusiform gyrus, and right thalamus (all p < 0.05, Bonferroni-corrected). A combination of variability in the lingual gyrus, PCG, and thalamus had optimal predictive value for distinguishing between the panic disorder and control groups (area under the curve = 0.776, sensitivity = 0.781, specificity = 0.732). In addition, the RPD subgroup showed significantly lower temporal variability in the left insula, right PCG, and bilateral lingual gyrus than the NRPD subgroup and control group (all p < 0.05, Bonferroni-corrected). Variability in the left insula and left lingual gyrus negatively correlated with the reduction rate of panic symptoms (all p < 0.05, Bonferroni-corrected). Functional brain images were collected only at baseline and may have been affected by medication use. Also, the follow-up period was only 2 weeks; sustained clinical remission may require longer follow-up. Combining lingual gyrus, PCG, and thalamus temporal variability alterations helped distinguish patients with panic disorder from healthy controls. The temporal variability in the insula and lingual gyrus are potential biomarkers for the treatment of panic disorder.

Predict Sarcopenia Risk in the Elderly by Cardiovascular Function and Heart Rate Variability

Objectives: Preventing and slowing sarcopenia in older people has become an important health issue. Heart rate variability reflects autonomic nervous system balance, and along with cardiovascular function, can indicate potential sarcopenia risk by signaling disruptions in muscle-supporting blood flow and autonomic control. Our objective was to collect simple and non-invasive cardiovascular function measurements and heart rate variability parameters to develop a model for predicting sarcopenia risk. Methods: We conducted a 3-minute cardiovascular function and heart rate variability test and sarcopenia screening (appendicular skeletal muscle index, grip strength, and walking speed) on 418 participants (105 males, 313 females, mean age 73.32±8.81 years) recruited from central Taiwan. Results: Appendicular skeletal muscle index, grip strength, walking speed, cardiovascular function, and heart rate variability had a significant correlation. The key features for predicting sarcopenia risk with logistic regression analysis were age, reflection index, dicrotic elasticity index, and high-frequency power (the overall accuracy was 70.10%; sensitivity was 81.30%; specificity was 54.07%). Conclusions: Simple and non-invasive 3-minute cardiovascular function and heart rate variability test parameters significantly predict sarcopenia risk in older people. This model can be applied to technology devices to detect sarcopenia risk and prevent sarcopenia in older people.

Optimization of functional diagnostic test: the effect of kernel method as an estimator of ROC curve

Technical development over the last few decades has resulted in the emergence of complex data, in many cases functional data (FD). This type of data can emerge in many medical studies which are geared towards detecting diseases, predicting their course or evaluating the response to a therapy, to name a few. Thus, it is very useful to have statistical methods enabling us to evaluate diagnostic tests based on functional biomarkers. In fact, a diagnostic test that uses functional variables as biomarkers has been developed recently. Their authors proposed a functional version of ROC analysis, resulting in an empirical estimate of the functional ROC curve. In order to improve this methodology, the present paper proposes a procedure to obtain a smooth version of non-parametric estimator of the ROC curve. In addition, a comprehensive simulation study lets to investigate the discriminatory and predictive abilities of the resulting functional diagnostic test. Two examples with real medical data illustrate the approach developed: one deals with gene expression levels for tumoural/normal samples of prostate cancer; the other dataset is about white matter structures in the brain in multiple sclerosis patients.

Weak Convergence of the Conditional Set-Indexed Empirical Process for Missing at Random Functional Ergodic Data

This work examines the asymptotic characteristics of a conditional set-indexed empirical process composed of functional ergodic random variables with missing at random (MAR). This paper’s findings enlarge the previous advancements in functional data analysis through the use of empirical process methodologies. These results are shown under specific structural hypotheses regarding entropy and under appealing situations regarding the model. The regression operator’s asymptotic (1−α)-confidence interval is provided for 0&lt;α&lt;1 as an application. Additionally, we offer a classification example to demonstrate the practical importance of the methodology.

Cognitive reserve, depressive symptoms, obesity, and change in employment status predict mental processing speed and executive function after COVID-19.

The risk factors for post-COVID-19 cognitive impairment have been poorly described. This study aimed to identify the sociodemographic, clinical, and lifestyle characteristics that characterize a group of post-COVID-19 condition (PCC) participants with neuropsychological impairment. The study sample included 426 participants with PCC who underwent a neurobehavioral evaluation. We selected seven mental speed processing and executive function variables to obtain a data-driven partition. Clustering algorithms were applied, including K-means, bisecting K-means, and Gaussian mixture models. Different machine learning algorithms were then used to obtain a classifier able to separate the two clusters according to the demographic, clinical, emotional, and lifestyle variables, including logistic regression with least absolute shrinkage and selection operator (LASSO) (L1) and Ridge (L2) regularization, support vector machines (linear/quadratic/radial basis function kernels), and decision tree ensembles (random forest/gradient boosting trees). All clustering quality measures were in agreement in detecting only two clusters in the data based solely on cognitive performance. A model with four variables (cognitive reserve, depressive symptoms, obesity, and change in work situation) obtained with logistic regression with LASSO regularization was able to classify between good and poor cognitive performers with an accuracy and a weighted averaged precision of 72%, a recall of 73%, and an area under the curve of 0.72. PCC individuals with a lower cognitive reserve, more depressive symptoms, obesity, and a change in employment status were at greater risk for poor performance on tasks requiring mentalprocessing speedand executive function. Study registration: www.ClinicalTrials.gov , identifier NCT05307575.

Effect of Macitentan in Pulmonary Arterial Hypertension and the Relationship Between Echocardiography and cMRI Variables: REPAIR Echocardiography Sub-study Results.

The aim of this sub-study was to evaluate the relationship between echocardiography (echo) and cardiac magnetic resonance imaging (cMRI) variables and to utilize echo to assess the effect of macitentan on right ventricle (RV) structure and function. REPAIR (NCT02310672) was a prospective, multicenter, single-arm, open-label, 52-week, phase 4 study in pulmonary arterial hypertension (PAH) patients, which investigated the effect of macitentan 10mg as monotherapy, or in combination with a phosphodiesterase 5 inhibitor, on RV structure, function, and hemodynamics using cMRI and right heart catheterization. In this sub-study, patients were also assessed by echo at screening and at weeks 26 and/or 52. Post hoc correlation analyses between echo and cMRI variables were performed using Pearson's correlation coefficient, Spearman's correlation coefficient, and Bland-Altman analyses. The Echo sub-study included 45 patients. Improvements in echo-assessed RV stroke volume (RVSV), left ventricular SV (LVSV), LV end-diastolic volume (LVEDV), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), and in 2D global longitudinal RV strain (2D GLRVS) were observed at weeks 26 and 52 compared to baseline. There was a strong correlation between echo (LVSV, 2D GLRVS, and LVEDV) and cMRI variables, with a moderate correlation for RVSV. Bland-Altman analyses showed a good agreement for LVSV measured by echo versus cMRI, whereas an overestimation in echo-assessed RVSV was observed compared to cMRI (bias of -15mL). Hemodynamic and functional variables, as well as safety, were comparable between the Echo sub-study and REPAIR. A good relationship between relevant echo and cMRI parameters was shown. Improvements in RV structure and function with macitentan treatment was observed by echo, consistent with results observed by cMRI in the primary analysis of the REPAIR study. Echo is a valuable complementary method to cMRI, with the potential to non-invasively monitor treatment response at follow-up. REPAIR NCT02310672.

Association between accelerometry measured patterns of sedentary behaviors and functional status in older adults

BackgroundOlder adults are highly sedentary, and too much sedentary behavior (SB) is associated with negative health effects, but little is known about SB patterns and their associations with functional status.AimsTo examine the association between objectively measured sedentary behavior time (SBT) and sedentary behavior fragmentation (SBF) and functional status in older adults using the National Health Aging Trends Study (NHATS) dataset, a nationally representative sample from 2021.MethodsData from NHATS were analyzed using weighted linear regressions to examine the association between objective measures of SBT (mean hours spent in SB/day during waking hours) and SBF, and six functional variables (difficulties with activities of daily living [ADL], short physical performance battery, hand grip strength, immediate word recall, delayed word recall, and mental health), accounting for sociodemographic, body mass index, and the number of chronic conditions.ResultsA total of 738 individuals from the NHATS were included. Higher SBT was associated with greater difficulties with ADL, poorer short physical performance battery and hand grip strength, lower scores in both immediate and delayed word recall, and poorer mental health. Higher SBF was associated with fewer difficulties with ADL, better short physical performance battery and hand grip strength, a higher score in immediate word recall, and better mental health.Discussionand conclusionsGreater fragmentation of SB was associated with better function, and increasing SBF may be a useful strategy for mitigating the effects of SB in older adults, but prospective research is needed to support this approach.

Clinical, tomographic and functional comparison of sporadic and tuberous sclerosis complex-associated forms of lymphangioleiomyomatosis: a retrospective cohort study.

Lymphangioleiomyomatosis (LAM) is a rare disease that can occur sporadically (S-LAM) or associated with the tuberous sclerosis complex (TSC-LAM). The natural history of LAM is not completely understood, including whether there is a difference between the clinical courses of the two forms. This study aimed to compare the clinical, functional and tomographic features between S-LAM and TSC-LAM, and evaluate the annual rates of change in lung function. This retrospective cohort study included patients with LAM followed up between 1994 and 2019. Clinical, functional and imaging variables were evaluated, and the lung cysts were automatically quantified. Quality of life and predictors of lung function impairment were accessed, and the annual rate of lung function decline was compared between S-LAM and TSC-LAM. Of the 107 patients included, 77 had S-LAM and 30 had TSC-LAM. Although patients with TSC-LAM had a higher prevalence of renal angiomyolipomas and neurological and dermatological manifestations, pulmonary function tests were similar. Patients with S-LAM had a greater rate of forced expiratory volume in 1 s decline and a higher extent of cysts. Pneumothorax, desaturation in the 6-minute walking test and a higher extent of lung cysts were predictors of functional impairment. A greater impact on vitality and emotional health was observed in the TSC-LAM. Greater functional decline and a higher cystic extension were found in patients with S-LAM. Our study provides a broad clinical, functional and tomographic characterisation of patients with LAM, adding valuable information to the existing evidence to better understand the two forms of the disease.

P007 Neutrophil function in lesional biopsies is a strong determinant of IBD severity and may relate to an altered functional state already present in circulating cells

Abstract Background Neutrophils clear luminal bacteria from the intestinal lamina propria and have a protective role in Inflammatory Bowel Disease (IBD). However, their production of inflammatory cytokines, matrix metalloproteases and radical oxygen species causes irreversible tissue damage. Histological assessment of infiltrating neutrophils and indirect measurement of neutrophil-derived calprotectin in feces are used to assess disease severity in patients. Since IBD is a heterogeneous disease in terms of presentation, severity and course, we hypothesize that different patients have a different composition of their neutrophil compartment that leads to a different balance between protection and damage. We aim to study the variability in neutrophil phenotype and function and relate it to patient heterogeneity. Methods We analyzed endoscopic biopsies and peripheral blood samples from children diagnosed with IBD within the PIBD-SETQ cohort. Paired biopsies obtained at diagnosis were scored by a pathologist and analyzed by IHC and RNAseq. RNAseq was also performed on purified circulatory neutrophil at diagnosis and their phenotype was analyzed by whole-blood flow cytometry. Results At diagnosis, high numbers of infiltrating neutrophils in intestinal tissue differentiated IBD patients with high clinical disease activity, more severe endoscopic and histological disease and high plasma concentrations of IL-17. RNA sequencing of lesional intestinal biopsies revealed differential expression of genes linked to neutrophil degranulation and IL-17 signaling in the colon of IBD patients with high neutrophil infiltration. Moreover, these biopsies had high mRNA expression for Oncostatin M, a neutrophil product known to associate with therapy resistance. To assess whether circulating neutrophils were altered in IBD before entering the intestinal tissue, we performed bulk RNAseq analysis of purified circulating neutrophils from non-IBD and CD patients. Neutrophils from CD patients had increased expression of genes related to granule formation and filling (MMP9, S100A8, S100A9) and pathogen sensing (TLR5, NLRC4) but not cytokine production (IL1B, OSM), relative to non-IBD patients. Expression of CD10 was decreased in circulating neutrophils from UC and CD patients while CD16 expression was lower in UC-derived neutrophils, suggesting these cells have a more immature state. Conclusion We have detected changes in the maturity of neutrophils in the circulation of some IBD patients that could have functional consequences in terms of bacterial clearance and tissue damage in the intestinal mucosa. Uncovering different functional profiles in neutrophils may help dissect patient heterogeneity and provide novel targets for therapy.