493 research outputs found

    Hazards to avoid in future neonatal studies of nasal high‑frequency oscillatory ventilation: lessons from an early terminated trial

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    OBJECTIVE: To investigate whether nasal high-frequency oscillatory ventilation (nHFOV) started immediately after extubation of mechanically ventilated very low birth weight infants reduces the partial pressure of carbon dioxide at 72 h after extubation in comparison with nasal continuous positive airway pressure. This randomised controlled single-centre trial aimed to include 68 preterm infants at high risk of extubation failure. RESULTS: Implementation of the study protocol was feasible. However, from 2015 to 2017, only six patients could be recruited, leading to early termination of the trial. The slow recruitment was due to the introduction of new strategies to avoid endotracheal mechanical ventilation, which reduced the number of eligible infants. Moreover, the included infants failed their extubation more often than anticipated, thereby increasing the required sample size. Based on our single-centre experience, we provide information for study planning and discuss the specific requirements for future trial protocols on nHFOV. The extubation of high-risk infants into nHFOV could well be beneficial, but a multicentric approach is necessary to investigate this hypothesis. Trial Registration Clinicaltrials.gov NCT02340299, on 16 January 2015

    Programming of embryonic development

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    Assisted reproductive techniques (ART) and parental nutritional status have profound effects on embryonic/fetal and placental development, which are probably mediated via “programming” of gene expression, as reflected by changes in their epigenetic landscape. Such epigenetic changes may underlie programming of growth, development, and function of fetal organs later in pregnancy and the offspring postnatally, and potentially lead to long-term changes in organ structure and function in the offspring as adults. This latter concept has been termed developmental origins of health and disease (DOHaD), or simply developmental programming, which has emerged as a major health issue in animals and humans because it is associated with an increased risk of non-communicable diseases in the offspring, including metabolic, behavioral, and reproductive dysfunction. In this review, we will briefly introduce the concept of developmental programming and its relationship to epigenetics. We will then discuss evidence that ART and periconceptual maternal and paternal nutrition may lead to epigenetic alterations very early in pregnancy, and how each pregnancy experiences developmental programming based on signals received by and from the dam. Lastly, we will discuss current research on strategies designed to overcome or minimize the negative consequences or, conversely, to maximize the positive aspects of developmental programming

    Bone Loss in Diabetes: Use of Antidiabetic Thiazolidinediones and Secondary Osteoporosis

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    Clinical evidence indicates that bone status is affected in patients with type 2 diabetes mellitus (T2DM). Regardless of normal or even high bone mineral density, T2DM patients have increased risk of fractures. One class of antidiabetic drugs, thiazolidinediones (TZDs), causes bone loss and further increases facture risk, placing TZDs in the category of drugs causing secondary osteoporosis. Risk factors for development of TZD-induced secondary osteoporosis are gender (women), age (elderly), and duration of treatment. TZDs exert their antidiabetic effects by activating peroxisome proliferator-activated receptor-Îł (PPAR-Îł) nuclear receptor, which controls glucose and fatty acid metabolism. In bone, PPAR-Îł controls differentiation of cells of mesenchymal and hematopoietic lineages. PPAR-Îł activation with TZDs leads to unbalanced bone remodeling: bone resorption increases and bone formation decreases. Laboratory research evidence points toward a possible separation of unwanted effects of PPAR-Îł on bone from its beneficial antidiabetic effects by using selective PPAR-Îł modulators. This review also discusses potential pharmacologic means to protect bone from detrimental effects of clinically used TZDs (pioglitazone and rosiglitazone) by using combinational therapy with approved antiosteoporotic drugs, or by using lower doses of TZDs in combination with other antidiabetic therapy. We also suggest a possible orthopedic complication, not yet supported by clinical studies, of delayed fracture healing in T2DM patients on TZD therapy

    Radiocarbon dating of modern peat profiles: Pre- and post-bomb C-14 variations in the construction of age-depth models

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    We present studies of 9 modern (up to 400-yr-old) peat sections from Slovenia, Switzerland, Austria, Italy, and Finland. Precise radiocarbon dating of modern samples is possible due to the large bomb peak of atmospheric 14C concentration in 1963 and the following rapid decline in the 14C level. All the analyzed 14C profiles appeared concordant with the shape of the bomb peak of atmospheric 14C concentration, integrated over some time interval with a length specific to the peat section. In the peat layers covered by the bomb peak, calendar ages of individual peat samples could be determined almost immediately, with an accuracy of 23 yr. In the pre-bomb sections, the calendar ages of individual dated samples are determined in the form of multi-modal probability distributions of about 300 yr wide (about AD 16501950). However, simultaneous use of the post-bomb and pre-bomb 14C dates, and lithological information, enabled the rejection of most modes of probability distributions in the pre-bomb section. In effect, precise age-depth models of the post-bomb sections have been extended back in time, into the wiggly part of the 14C calibration curve

    A pilot study comparing the metabolic profiles of elite-level athletes from different sporting disciplines

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    Background: The outstanding performance of an elite athlete might be associated with changes in their blood metabolic profile. The aims of this study were to compare the blood metabolic profiles between moderate- and high-power and endurance elite athletes and to identify the potential metabolic pathways underlying these differences. Methods: Metabolic profiling of serum samples from 191 elite athletes from different sports disciplines (121 high- and 70 moderate-endurance athletes, including 44 high- and 144 moderate-power athletes), who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between high- and moderate-power and endurance sports were assessed by univariate linear models. Results: Out of 743 analyzed metabolites, gamma-glutamyl amino acids were significantly reduced in both high-power and high-endurance athletes compared to moderate counterparts, indicating active glutathione cycle. High-endurance athletes exhibited significant increases in the levels of several sex hormone steroids involved in testosterone and progesterone synthesis, but decreases in diacylglycerols and ecosanoids. High-power athletes had increased levels of phospholipids and xanthine metabolites compared to moderate-power counterparts. Conclusions: This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites. Replication studies are warranted to confirm differences in the metabolic profiles associated with athletes’ elite performance in independent data sets, aiming ultimately for deeper understanding of the underlying biochemical processes that could be utilized as biomarkers with potential therapeutic implications

    Slow pyrolysis of organic fraction of municipal solid waste (OFMSW): Characterisation of products and screening of the aqueous liquid product for anaerobic digestion

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    A comprehensive study of the energy yield from slow pyrolysis of the organic fraction of municipal solid waste (OFMSW) and energy recovery from the aqueous liquid product by anaerobic digestion has been carried out. In this paper, the results of the liquid pyrolysis product characterisation are presented, with toxicity and methane potential assessments of the aqueous liquid product. The OFMSW feedstock was obtained from a UK waste treatment plant. Shredded samples dried to different moisture contents (12.7–45.8%) were processed in a 300 g per hour auger screw pyrolysis reactor at temperatures from 450 to 850 °C. Sixteen pyrolysis runs were performed, with process mass balance closures above 90% obtained (wet feed basis). Pyrolysis liquids showed clear phase separation under gravity. With increasing processing temperature, the liquid yield (both organic and aqueous fraction) reduced but the gas yield increased. An investigation into the product energy distribution indicated that processing temperature had a strong effect on the product energy distribution, while the effect of feedstock moisture was relatively small. Batch anaerobic testing of the aqueous fraction showed that toxicity increased with pyrolysis processing temperature and decreased with feedstock moisture content. Statistical analysis confirmed that the pyrolysis processing temperature was the dominant factor affecting the toxicity of the aqueous product. Careful acclimatisation of the microbial consortium to the applied substrate and loading is likely to be necessary for improved digestion of the aqueous fraction
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