Search

OBJECTIVE: Recent studies demonstrated that current European Respiratory Society/American Thoracic Society spirometric reference equations, used in general population, may not be applicable in population of elite athletes. Although it is well known that physical activity may affect lung volumes, the effect of sporting activity on pulmonary function testing indices was never examined. The aim of this study was to examine the differences in functional respiratory parameters in various types of sports by measuring lung volumes and to extend the existing factors as well as sport disciplines which affect respiratory function the most. SUBJECTS AND METHODS: A total of 1639 elite male athletes, aged 18-35 years were divided in 4 groups according to the predominant characteristics of training: skill, power, mixed and endurance athletes. They performed basic anthropometric measurements and spirometry. Groups were compared, and Pearson's simple correlation was performed to test the relation between anthropometric and spirometric characteristics of athletes. RESULTS: All anthropometric characteristics significantly differed among groups and correlate with respiratory parameters. The highest correlation was found for body height and weight. CONCLUSIONS: Sports participation is associated with respiratory adaptation, and the extent of adaptation depends on type of activity. Endurance sports athletes have higher lung volumes in comparison with skill, mixed and power group of sport. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformations (CCMs) are anomalies of the cerebral vasculature. Loss of the CCM proteins CCM1/KRIT1, CCM2, or CCM3/PDCD10 trigger a MAPK-Krüppel-like factor 2 (KLF2) signaling cascade, which induces a pathophysiological pattern of gene expression. The downstream target genes that are activated by KLF2 are mostly unknown. Here we show that Chromobox Protein Homolog 7 (CBX7), component of the Polycomb Repressive Complex 1, contributes to pathophysiological KLF2 signaling during zebrafish cardiovascular development. CBX7/cbx7a mRNA is strongly upregulated in lesions of CCM patients, and in human, mouse, and zebrafish CCM-deficient endothelial cells. The silencing or pharmacological inhibition of CBX7/Cbx7a suppresses pathological CCM phenotypes in ccm2 zebrafish, CCM2-deficient HUVECs, and in a pre-clinical murine CCM3 disease model. Whole-transcriptome datasets from zebrafish cardiovascular tissues and human endothelial cells reveal a role of CBX7/Cbx7a in the activation of KLF2 target genes including TEK, ANGPT1, WNT9, and endoMT-associated genes. Our findings uncover an intricate interplay in the regulation of Klf2-dependent biomechanical signaling by CBX7 in CCM. This work also provides insights for therapeutic strategies in the pathogenesis of CCM., (© 2024. The Author(s).)

Induced pluripotent stem cell (iPSC) derived endothelial cells (iECs) have emerged as a promising tool for studying vascular biology and providing a platform for modelling various vascular diseases, including those with genetic origins. Currently, primary ECs are the main source for disease modelling in this field. However, they are difficult to edit and have a limited lifespan. To study the effects of targeted mutations on an endogenous level, we generated and characterized an iPSC derived model for venous malformations (VMs). CRISPR-Cas9 technology was used to generate a novel human iPSC line with an amino acid substitution L914F in the TIE2 receptor, known to cause VMs. This enabled us to study the differential effects of VM causative mutations in iECs in multiple in vitro models and assess their ability to form vessels in vivo. The analysis of TIE2 expression levels in TIE2 L914F iECs showed a significantly lower expression of TIE2 on mRNA and protein level, which has not been observed before due to a lack of models with endogenous edited TIE2 L914F and sparse patient data. Interestingly, the TIE2 pathway was still significantly upregulated and TIE2 showed high levels of phosphorylation. TIE2 L914F iECs exhibited dysregulated angiogenesis markers and upregulated migration capability, while proliferation was not affected. Under shear stress TIE2 L914F iECs showed reduced alignment in the flow direction and a larger cell area than TIE2 WT iECs. In summary, we developed a novel TIE2 L914F iPSC-derived iEC model and characterized it in multiple in vitro models. The model can be used in future work for drug screening for novel treatments for VMs., (© 2024. The Author(s).)

Introduction: The Asthma Control Questionnaire (ACQ) is a seven-item questionnaire assessing symptoms that asthma clinicians consider to be most important for evaluating the adequacy of asthma control. An online version of the ACQ may be able to indicate whether a visit to the physician is warranted to modify therapy to achieve better control of their asthma, ultimately reducing the number of unnecessary visits, particularly during the pandemic. The aim of our study is to compare the paper and online ACQ to validate the online version for use in real-life settings. Methods: Our study included 28 patients who completed both paper and the online ACQ on the same day when they came home. The online version of the questionnaire was prepared to look similar to the paper form, with the same sentences and answers. Results: The correlation between paper and online ACQ questionnaires was very high ( r  = 0.935; p  < 0.001). When comparing each individual item, correlation coefficients ranged from 0.672 to 0.935. The lowest correlation is obtained in activity limitations, while the next one is 0.767, others higher than 0.8. The online form gave small and insignificantly higher scores compared to paper form with mean difference between -0.07 and 0.21. Mean difference of 0.01 ( p  = 0.986) between paper ACQ and online ACQ is obtained. Conclusion: The online version of the ACQ can be used for asthma control monitoring in pediatric patients in order to minimize unnecessary social contacts as well as hospital patient load, but retain adequate surveillance of disease symptoms by their physician.

Apolipoprotein L1 (APOL1) high-risk genotypes are associated with increased risk of chronic kidney disease (CKD) in people of West African ancestry. Given the importance of endothelial cells (ECs) in CKD, we hypothesized that APOL1 high-risk genotypes may contribute to disease via EC-intrinsic activation and dysfunction. Single cell RNA sequencing (scRNA-seq) analysis of the Kidney Precision Medicine Project dataset revealed APOL1 expression in ECs from various renal vascular compartments. Utilizing two public transcriptomic datasets of kidney tissue from African Americans with CKD and a dataset of APOL1-expressing transgenic mice, we identified an EC activation signature; specifically, increased intercellular adhesion molecule 1 (ICAM-1) expression and enrichment in leukocyte migration pathways. In vitro , APOL1 expression in ECs derived from genetically modified human induced pluripotent stem cells and glomerular ECs triggered changes in ICAM-1 and platelet endothelial cell adhesion molecule 1 (PECAM-1) leading to an increase in monocyte attachment. Overall, our data suggest the involvement of APOL1 as an inducer of EC activation in multiple renal vascular beds with potential effects beyond the glomerular vasculature., Competing Interests: M.C., E.E., R.A., A.F., K.B-M., A.S., J.C., H.K.G, B.L., R.H., L.B., P.J.G., and M.L. are all AstraZeneca employees., (© 2023 The Authors.)

Introduction: Over the past few years, there has been an increase in lung and diaphragm ultrasound applications as a tool to evaluate the outcomes and settings of noninvasive respiratory supports. However, actual clinical practices in this field are yet to be known. The aim of this study was to investigate the current clinical utilization of ultrasound for noninvasive respiratory supports on an international level., Materials and Methods: The study employed an online survey consisting of 32 items, which was sent via email to intensivists, pulmonologists, emergency medicine physicians, and other specialists with expertise in using ultrasound and/or noninvasive respiratory supports., Result: We collected 52 questionnaires. The ultrasound study of diaphragm dysfunction was well-known by the majority of respondents (57.7%). Diaphragm performance was used as a weaning failure predictor (48.5%), as a predictor of noninvasive ventilation failure (38.5%) and as a tool for the ventilator settings adjustment (30.8%). In patients with acute respiratory failure, 48.1% used ultrasound to assess the damaged lung area to set up ventilatory parameters, 34.6% to monitor it after noninvasive ventilation application, and 32.7% to match it with the ventilatory settings for adjustment purposes. When administering high flow nasal cannula - oxygen therapy, 42.3% of participants used ultrasound to evaluate lung involvement and assess flow parameters., Conclusions: Lung and diaphragm ultrasound is an established clinical practice to evaluate noninvasive respiratory supports outcomes and settings. Further studies are needed to evaluate the educational aspects to increase confidence and indications for its use.

The first application of modern non-invasive mechanical ventilation (NIV) can be traced back to over 30 years ago when a patient suffering from Duchenne Muscular Dystrophy was successfully ventilated. Since then, the use of NIV has been on the rise throughout the world. Although a very modern and safe therapy, complications during its application are inevitable. In addition to some well-known complications, others have described more rare entities. In this article, we described such rare complications as pneumoperitoneum, pneumocephalus, parotitis, gastric perforation, and barotrauma. The purpose of this review was to describe unusual complications of NIV, their prevalence, and the mechanisms by which such complications arise. We performed a clinical review by searching PubMed, Embase, and Cochrane libraries with Mesh terms: 'non-invasive mechanical ventilation', 'high-flow nasal cannula', 'rare complication', 'unusual complication', and 'unexpected complication'. These terms were cross-referenced with other keywords: 'pneumoperitoneum', 'parotitis', 'pneumocephalus', 'gastric insufflation', and 'barotrauma'. We included 26 research papers. When applying mechanical ventilation, it is necessary to have a strong knowledge of the mechanics of the device as well as familiarity with the complications that may occur during its use, including less common ones. Prompt and effective treatment of such complications is required, as well as careful consideration of the potential causes of such events, during the application of NIV or HFNC.

Prokaryotic restriction enzymes, recombinases and Cas proteins are powerful DNA engineering and genome editing tools. However, in many primary cell types, the efficiency of genome editing remains low, impeding the development of gene- and cell-based therapeutic applications. A safe strategy for robust and efficient enrichment of precisely genetically engineered cells is urgently required. Here, we screen for mutations in the receptor for Diphtheria Toxin (DT) which protect human cells from DT. Selection for cells with an edited DT receptor variant enriches for simultaneously introduced, precisely targeted gene modifications at a second independent locus, such as nucleotide substitutions and DNA insertions. Our method enables the rapid generation of a homogenous cell population with bi-allelic integration of a DNA cassette at the selection locus, without clonal isolation. Toxin-based selection works in both cancer-transformed and non-transformed cells, including human induced pluripotent stem cells and human primary T-lymphocytes, as well as it is applicable also in vivo, in mice with humanized liver. This work represents a flexible, precise, and efficient selection strategy to engineer cells using CRISPR-Cas and base editing systems.

Objective: Distal radius fracture (DRF) is one of the most frequent population fracture mostly affecting women, and frequently leading to complex regional pain syndrome (CRPS). Management of DRF and CRPS in gerontology is complex. The aim was to evaluate the use of polarized, polychromatic, low-energy light therapy combined with conventional treatment after DRF in gerontology and to follow up patients for CRPS emergence. Materials and methods: After plaster removal, female patients ( n  = 52) were divided into two groups. Group 1 ( n  = 26) was treated with exercises and cryotherapy on the wrist and dorsal hand (control). Group 2 ( n  = 26) was additionally treated with light therapy (Bioptron). Results: While pain decreased and supination and pronation improved in all patients after 15 days of therapy, pain reduction was accelerated and supination enhanced in the light therapy-treated group ( p  < 0.05). None of the patients in the light therapy-treated group developed CRPS during the 6-month follow-up, compared with four patients (15.4%) in the control group ( p  < 0.05). Complete hand fist-forming capacity was achieved in 19 patients (73.1%) in the light therapy-treated group compared with 16 patients (61.5%) in the control group ( p  > 0.05). Conclusions: Bioptron light therapy combined with conventional therapy improves patient outcome after DRF in gerontology, compared with conventional treatment alone.

Background: The influence of exercise on the pulmonary function is controverse, some studies have reported no sports influence, while the others have found positive correlation., Aim: To evaluate and compare the sports influence on pulmonary function: spirometry (VC, FVC, FEV1, FEV1/FVC), lung diffusing capacity (DLCO) and coefficient of the CO gas transfer (KCO) in two elite athletes groups and healthy sedentary controls., Method: Equally divided into aerobic and anaerobic group, 60 elite athletes were recruited, as well as 43 age-matched, healthy sedentary controls. All of the participants performed basic anthropometric measurements, spirometry, DLCO and KCO at rest. Kruskal-Wallis one way ANOVA test was used to determine differences between groups; Mann-Whitney U test was used for inter-groups differences and Pearson coefficient for pulmonary variables and anthropometric parameters correlation. Statistical analyses were performed using the SPSS computer statistic program, version 20., Results: No differences were found in pulmonary characteristics (spirometric function values, DLCO and KCO) in athletes and non-athletes at rest, as well as between aerobics and anaerobics. There were no correlations between the anthropometric parameters and the investigated respiratory function tests. DLCO (%) correlated positively with height in athletes playing anaerobic type of sport (karate and taekwondo) (p=0.036; r=0.544), and negatively in sedentary control group (p=0.030; r=-0.560). Regarding KCO, no differences were found., Conclusion: Spirometry indices and DLCO are not influenced either by aerobic or anaerobic training type, so benefits of sports on pulmonary indices or DLCO was not confirmed., (Copyright © 2017 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Relationship between physical activity and mental disorders in late pregnancy is unclear. In this work, we demonstrate that there is a significant association between the time spent on walking and symptoms of depression and anxiety in antenatal period. The cross-sectional study was done on a sample of 200 healthy women in 9th month of physiological pregnancy at Health center Kraljevo, Serbia during 2015. Each participant was given a questionnaire consisting of general questions regarding physical activity, pregnancy, and other parameters. Also, each participant completed a Beck depression inventory (BDI) and Zung anxiety scale (ZAS). There was a statistically significant negative correlation (p<0.05) between the BDI score and the daily time spent on walking. There was also a strong positive connection between the daily time spent on walking and level of anxiety (p<0.01). To our knowledge this is the first study to jointly test the relationship between scores of Beck depression inventory and Zung anxiety scale, and time spent on walking as physical activity in antenatal period. The results represent the basis for further research in the field of gynecological psychology, psychiatry and behavioral physiology., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The major oxygen sensors in the human body are peripheral chemoreceptors. also known as interoreceptors- as connected with internal organs, located in the aortic arch and in the body of the common carotid artery. Chemoreceptor function under physiological conditions. Stimulation of peripheral chemoreceptors during enviromental hypoxia causes a reflex-mediated increased ventilation, followed by the increase of the muscle sympatic activity, aiming to maintain tissue oxygen homeostatis, as well as glucosae, homeostatis. Besides that, peripheral chemoreceptors interact with central chemoreceptors. responsible for carbon dioxide changes . and they are able to modulate each other. Chemoreceptor function in pathophysiological conditions. Investigations of respiratory function in many pathological processes, such as hypertension, obstructive sleep apnea, congestive heart failure and many other diseases that are presented with enhanced peripheral chemosensitivity and impaired functional sy mpatholysis ultimately determine the peripheral chemorcceptor role and significance of peripheral chemoreceptors in the process of those pathological conditions development. Considering this, the presumed influence of peripheral chemoreceptors is important in patients having the above mentioned pathology., Conclusion: The importance and the role of peripheral chemoreceptors in the course of the breathing control is still controversial, despite many scientific attempts to solve this problem. The main objective of this review is to give the latest data on the peripheral chemoreceptor role and to highlight the importance of peripheral chemoreceptors for maintaining of oxygen homeostasis in pateints with hypoxia caused by either physiological or pathological conditions.

Objective: To examine differences in lung function among sports that are of a similar nature and to determine which anthropometric/demographic characteristics correlate with lung volumes and flows., Methods: This was a cross-sectional study involving elite male athletes (N = 150; mean age, 21  4 years) engaging in one of four different sports, classified according to the type and intensity of exercise involved. All athletes underwent full anthropometric assessment and pulmonary function testing (spirometry)., Results: Across all age groups and sport types, the elite athletes showed spirometric values that were significantly higher than the reference values. We found that the values for FVC, FEV1, vital capacity, and maximal voluntary ventilation were higher in water polo players than in players of the other sports evaluated (p < 0.001). In addition, PEF was significantly higher in basketball players than in handball players (p < 0.001). Most anthropometric/demographic parameters correlated significantly with the spirometric parameters evaluated. We found that BMI correlated positively with all of the spirometric parameters evaluated (p < 0.001), the strongest of those correlations being between BMI and maximal voluntary ventilation (r = 0.46; p < 0.001). Conversely, the percentage of body fat correlated negatively with all of the spirometric parameters evaluated, correlating most significantly with FEV1 (r = -0.386; p < 0.001)., Conclusions: Our results suggest that the type of sport played has a significant impact on the physiological adaptation of the respiratory system. That knowledge is particularly important when athletes present with respiratory symptoms such as dyspnea, cough, and wheezing. Because sports medicine physicians use predicted (reference) values for spirometric parameters, the risk that the severity of restrictive disease or airway obstruction will be underestimated might be greater for athletes.

Non-invasive ventilation performed through an oronasal mask is a standard in clinical and homecare mechanical ventilation. Besides all its advantages, inevitable leaks through the mask cause errors in the feedback information provided by the airflow sensor and, hence, patient-ventilator asynchrony with multiple negative consequences. Here we investigate a new way to provide a trigger to the ventilator. The method is based on the measurement of rib cage movement at the onset of inspiration and during breathing by fibre-optic sensors. In a series of simultaneous measurements by a long-period fibre grating sensor and pneumotachograph we provide the statistical evidence of the 200 ms lag of the pneumo with respect the fibre-optic signal. The lag is registered consistently across three independent delay metrics. Further, we discuss exceptions from this trend and identify the needed improvements to the proposed fibre-sensing scheme.

Objectives: Hypertension is one of the most prevalent cardiovascular disorders in athletes. The aims of our study were to assess the impact of elevated blood pressure (BP) on exercise capacity in athletes and evaluate the differences in left ventricular structure and function., Methods: Elite male athletes (n=517, aged 23±5years) underwent Doppler echocardiography with tissue Doppler imaging. Diastolic function was assessed by measuring peak early and late transmitral (E and A) and annular diastolic filling velocities (e' and a'). Maximal cardiopulmonary exercise testing was performed to measure maximal oxygen consumption (VO2max), ventilatory anaerobic threshold (VAT) and heart rate reserve (HRR). After BP measurement, they were grouped according to the ESH/ESC guidelines on: optimal (OBP), normal (NBP), high normal BP (HNBP), and hypertensive (HT)., Results: We found significantly lower VO2max, VAT and HRR in the groups with HNBP and HT, after the adjustment for the type of sport, body fat content and age. There was an increasing trend in resting HR among groups (p<0.001). Although none of the subjects had impaired diastolic function, the HT group had higher left atrial volume, and lower e' and e'/a'. Resting systolic BP (p<0.05), HR (p<0.001), HRR (p<0.001) and e'/a' (p<0.01) independently predicted VO2max. Indexes E/e' and e'/a' were associated with resting systolic BP (p<0.05)., Conclusion: Even in the absence of structural or functional heart damage, elevated BP in elite athletes, together with the presence of autonomic dysfunction, leads to decrease in exercise capacity. Staging of hypertension according to the BP level, on the one hand, and reflexion of BP on cardiopulmonary capacity, on the other, may be coupled for further risk stratification., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)