335 research outputs found

    Effect of an eight-week high-intensity interval training programme on circulating sphingolipid levels in middle-aged adults at elevated cardiometabolic risk (SphingoFIT)-Protocol for a randomised controlled exercise trial.

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    Evidence indicates that sphingolipid accumulation drives complex molecular alterations promoting cardiometabolic diseases. Clinically, it was shown that sphingolipids predict cardiometabolic risk independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, little is known about therapeutic modalities to lower sphingolipid levels. Exercise, a powerful means to prevent and treat cardiometabolic diseases, is a promising modality to mitigate sphingolipid levels in a cost-effective, safe, and patient-empowering manner. This randomised controlled trial will explore whether and to what extent an 8-week fitness-enhancing training programme can lower serum sphingolipid levels of middle-aged adults at elevated cardiometabolic risk (n = 98, 50% females). The exercise intervention will consist of supervised high-intensity interval training (three sessions weekly), while the control group will receive physical activity counselling based on current guidelines. Blood will be sampled early in the morning in a fasted state before and after the 8-week programme. Participants will be provided with individualised, pre-packaged meals for the two days preceding blood sampling to minimise potential confounding. An 'omic-scale sphingolipid profiling, using high-coverage reversed-phase liquid chromatography coupled to tandem mass spectrometry, will be applied to capture the circulating sphingolipidome. Maximal cardiopulmonary exercise tests will be performed before and after the 8-week programme to assess patient fitness changes. Cholesterol, triglycerides, glycated haemoglobin, the homeostatic model assessment for insulin resistance, static retinal vessel analysis, flow-mediated dilatation, and strain analysis of the heart cavities will also be assessed pre- and post-intervention. This study shall inform whether and to what extent exercise can be used as an evidence-based treatment to lower circulating sphingolipid levels. The trial was registered on www.clinicaltrials.gov (NCT06024291) on August 28, 2023

    Self-Sufficient Formaldehyde-to-Methanol Conversion by Organometallic Formaldehyde Dismutase Mimic

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    The catalytic networks of methylotrophic organisms, featuring redox enzymes for the activation of one-carbon moieties, can serve as great inspiration in the development of novel homogeneously catalyzed pathways for the interconversion of C-1 molecules at ambient conditions. An imidazolium-tagged arene-ruthenium complex was identified as an effective functional mimic of the bacterial formaldehyde dismutase, which provides a new and highly selective route for the conversion of formaldehyde to methanol in absence of any external reducing agents. Moreover, secondary amines are reductively methylated by the organometallic dismutase mimic in a redox self-sufficient manner with formaldehyde acting both as carbon source and reducing agent

    Study protocol: an early intervention program to improve motor outcome in preterm infants: a randomized controlled trial and a qualitative study of physiotherapy performance and parental experiences

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    Background Knowledge about early physiotherapy to preterm infants is sparse, given the risk of delayed motor development and cerebral palsy. Methods/Design A pragmatic randomized controlled study has been designed to assess the effect of a preventative physiotherapy program carried out in the neonatal intensive care unit. Moreover, a qualitative study is carried out to assess the physiotherapy performance and parents' experiences with the intervention. The aim of the physiotherapy program is to improve motor development i.e. postural control and selective movements in these infants. 150 infants will be included and randomized to either intervention or standard follow-up. The infants in the intervention group will be given specific stimulation to facilitate movements based on the individual infant's development, behavior and needs. The physiotherapist teaches the parents how to do the intervention and the parents receive a booklet with photos and descriptions of the intervention. Intervention is carried out twice a day for three weeks (week 34, 35, 36 postmenstrual age). Standardized tests are carried out at baseline, term age and at three, six, 12 and 24 months corrected age. In addition eight triads (infant, parent and physiotherapist) are observed and videotaped in four clinical encounters each to assess the process of physiotherapy performance. The parents are also interviewed on their experiences with the intervention and how it influences on the parent-child relationship. Eight parents from the follow up group are interviewed about their experience. The interviews are performed according to the same schedule as the standardized measurements. Primary outcome is at two years corrected age. Discussion The paper presents the protocol for a randomized controlled trial designed to study the effect of physiotherapy to preterm infants at neonatal intensive care units. It also studies physiotherapy performance and the parent's experiences with the intervention

    A Melodic Contour Repeatedly Experienced by Human Near-Term Fetuses Elicits a Profound Cardiac Reaction One Month after Birth

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    Human hearing develops progressively during the last trimester of gestation. Near-term fetuses can discriminate acoustic features, such as frequencies and spectra, and process complex auditory streams. Fetal and neonatal studies show that they can remember frequently recurring sounds. However, existing data can only show retention intervals up to several days after birth.Here we show that auditory memories can last at least six weeks. Experimental fetuses were given precisely controlled exposure to a descending piano melody twice daily during the 35(th), 36(th), and 37(th) weeks of gestation. Six weeks later we assessed the cardiac responses of 25 exposed infants and 25 naive control infants, while in quiet sleep, to the descending melody and to an ascending control piano melody. The melodies had precisely inverse contours, but similar spectra, identical duration, tempo and rhythm, thus, almost identical amplitude envelopes. All infants displayed a significant heart rate change. In exposed infants, the descending melody evoked a cardiac deceleration that was twice larger than the decelerations elicited by the ascending melody and by both melodies in control infants.Thus, 3-weeks of prenatal exposure to a specific melodic contour affects infants 'auditory processing' or perception, i.e., impacts the autonomic nervous system at least six weeks later, when infants are 1-month old. Our results extend the retention interval over which a prenatally acquired memory of a specific sound stream can be observed from 3-4 days to six weeks. The long-term memory for the descending melody is interpreted in terms of enduring neurophysiological tuning and its significance for the developmental psychobiology of attention and perception, including early speech perception, is discussed

    Pharmacological inhibition of leukotrienes in an animal model of bleomycin-induced acute lung injury

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    Leukotrienes are increased locally in idiopathic pulmonary fibrosis. Furthermore, a role for these arachidonic acid metabolites has been thoroughly characterized in the animal bleomycin model of lung fibrosis by using different gene knock-out settings. We investigated the efficacy of pharmacological inhibition of leukotrienes activity in the development of bleomycin-induced lung injury by comparing the responses in wild-type mice with mice treated with zileuton, a 5-lipoxygenase inhibitor and MK-571, a cys-leukotrienes receptor antagonist. Mice were subjected to intra-tracheal administration of bleomycin or saline and were assigned to receive either MK-571 at 1 mg/Kg or zileuton at 50 mg/Kg daily. One week after bleomycin administration, BAL cell counts, lung histology with van Gieson for collagen staining and immunohistochemical analysis for myeloperoxidase, IL-1 and TNF-α were performed. Following bleomycin administration both MK-571 and zileuton treated mice exhibited a reduced degree of lung damage and inflammation when compared to WT mice as shown by the reduction of:(i) loss of body weight, (ii) mortality rate, (iii) lung infiltration by neutrophils (myeloperoxidase activity, BAL total and differential cell counts), (iv) lung edema, (v) histological evidence of lung injury and collagen deposition, (vi) lung myeloperoxidase, IL-1 and TNF-α staining. This is the first study showing that the pharmacological inhibition of leukotrienes activity attenuates bleomycin-induced lung injury in mice. Given our results as well as those coming from genetic studies, it might be considered meaningful to trial this drug class in the treatment of pulmonary fibrosis, a disease that still represents a major challenge to medical treatment
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