214 research outputs found
Postnatal adaptations of phosphatidylcholine metabolism in extremely preterm infants: implications for choline and PUFA metabolism
No full textBACKGROUND: Lipid metabolism in pregnancy delivers PUFAs from maternal liver to the developing fetus. The transition at birth to diets less enriched in PUFA is especially challenging for immature, extremely preterm infants who are typically supported by total parenteral nutrition. OBJECTIVE: The aim was to characterize phosphatidylcholine (PC) and choline metabolism in preterm infants and demonstrate the molecular specificity of PC synthesis by the immature preterm liver in vivo. METHODS: This MS-based lipidomic study quantified the postnatal adaptations to plasma PC molecular composition in 31 preterm infants <28 weeks' gestational age. Activities of the cytidine diphosphocholine (CDP-choline) and phosphatidylethanolamine-N-methyltransferase (PEMT) pathways for PC synthesis were assessed from incorporations of deuterated methyl-D9-choline chloride. RESULTS: The concentration of plasma PC in these infants increased postnatally from median values of 481 (IQR: 387-798) µM at enrollment to 1046 (IQR: 616-1220) µM 5 d later (P < 0.001). Direct incorporation of methyl-D9-choline demonstrated that this transition was driven by an active CDP-choline pathway that synthesized PC enriched in species containing oleic and linoleic acids. A second infusion of methyl-D9-choline chloride at day 5 clearly indicated continued activity of this pathway. Oxidation of D9-choline through D9-betaine resulted in the transfer of 1 deuterated methyl group to S-adenosylmethionine. A very low subsequent transfer of this labeled methyl group to D3-PC indicated that liver PEMT activity was essentially inactive in these infants. CONCLUSIONS: This study demonstrated that the preterm infant liver soon after birth, and by extension the fetal liver, was metabolically active in lipoprotein metabolism. The low PEMT activity, which is the only pathway for endogenous choline synthesis and is responsible for hormonally regulated export of PUFAs from adult liver, strongly supports increased supplementation of preterm parenteral nutrition with both choline and PUFAs
Convolutions Goss L-Series and Tensor Products of Drinfeld Modules
No full textWe present special value results of convolutions of Goss and Pellarin L-series attached to Drinfeld modules that take values in Tate algebras by Papanikolas and the author. Following the same framework, we establish special value results of convolutions of two Goss L-series attached to Drinfeld modules that take values in Fq(( 1/�� )). Applying the class module formula of Fang to tensor products of two Drinfeld modules, we provide special value formulas for their L-functions. By way of the theory of Schur polynomials these identities take the form of specializations of convolutions of Rankin-Selberg type. Finally, we show an explicit computation on regulators of tensor product as well as symmetric and alternating squares of Drinfeld modules, which appear in the Fang���s class module formula
Surfactant phospholipid kinetics in ventilated children after therapeutic surfactant supplementation
No full textAcute lung Injury leads to alterations in surfactant lipid composition and metabolism. Although several mechanisms contribute to dysregulated surfactant metabolism, studies investigating in vivo surfactant metabolism are limited. The aim of this study is to characterise surfactant phospholipid composition and flux utilising a stable isotope labelling technique in mechanically ventilated paediatric patients. Paediatric patients (<16 years of age) received 3.6 mg/kg intravenous methyl-D 9-choline chloride followed by the endotracheal instillation of 100 mg/kg of exogenous surfactant after 24 h. Bronchioalveolar fluid samples were taken at baseline and 12, 24, 36, 48, 72 and 96 h after methyl-D 9-choline infusion. Nine participants (median age of 48 days) were recruited. The primary phosphatidylcholine (PC) composition consisted of PC16:0/16:0 or DPPC (32.0 ± 4.5%). Surfactant supplementation resulted in a 30% increase in DPPC. Methyl-D 9 PC enrichment was detected after 12 h and differed significantly between patients, suggesting variability in surfactant synthesis/secretion by the CDP-choline pathway. Peak enrichment was achieved (0.94 ± 0.15% of total PC) at 24 h after methyl-D 9-choline infusion. There was a trend towards reduced enrichment with the duration of mechanical ventilation prior to study recruitment; however, this was not statistically significant (p = 0.19). In this study, we demonstrated the fractional molecular composition and turnover of surfactant phospholipids, which was highly variable between patients.</p
Molecular microbiological characterization of preterm neonatesat risk of bronchopulmonary dysplasia
No full textThe role of infection in bronchopulmonary dysplasia (BPD) is unknown. We present an observational study of 55 premature infants born weighing less than 1.3 kg within two level III neonatal intensive care units. Endotracheal aspirates (ETA) and nasogastric aspirates (NGA) were studied with denaturing gradient gel electrophoresis (DGGE) profiling to elucidate the total bacterial community, and species-specific PCR was used to detect the presence of Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum. DGGE identified bacterial species in 59% of NGA and ETA samples combined. A diverse range of species were identified including several implicated in preterm labor. Species-specific PCR identified M. hominis in 25% of NGA and 11% of ETA samples. Among the 48 infants surviving up to 36 wk-postconceptual age, ordinal logistic regression showed the odds ratio for BPD or death where Ureaplasma was present/absent as 4.80 (95% CI 1.15-20.13). After adjusting for number of days ventilated, this was reduced to 2.04 (0.41-10.25). These data demonstrate how the combined use of DGGE and species-specific PCR identifies a high exposure in utero and around the time of birth to bacteria that might be causally related to preterm delivery and subsequent lung injury.<br/
Designing for Healthy Eating Behaviour: A playful approach to preventing childhood obesity
No full textToday more deaths are linked to obesity and weight gain than famine and malnutrition, especially with children a concerning increase in global childhood obesity has developed. Currently, many programs have been implemented in the Netherlands to address childhood obesity, however, few go beyond awareness and involve a physical experience. To address this gap this project researched and designed a product experience to support families to develop a healthier relationship with food. The primary aim of the research was to gain a better understanding of how food, play, and parent-child interactions influence eating habits and behaviours in families, especially with regard to toddlers and younger children. Through this research a design was created for the year 2025 and tested with families.In the first phases of this project, research was conducted through a literature review and qualitative studies with domain experts as well as parents with children between the ages of 1 and 4. These research studies focused on gaining a deeper understanding of specific values, beliefs, and parental experiences within a family in order to better understand the conflicts that exist in the home food context. The insights gained through these studies were gathered and categorized based on how they contribute to what family interactions around food moments will look like in the year 2025. For example, one insight is that parents struggle to set clear boundaries; they often sacrifice their own well-being in order to be more engaged in their children’s lives. Most families are child-centred, where the children hold priority over their parent’s time, energy, and attention. When reviewing these categories, the need for flexibility was a surprising yet important concept.Once a clear formulation of the home food context was established a series of design interventions were developed and tested. Interventions were tested by myself as well as other families in order to identify and establish which designs positively influence our relationship with food. The design interventions were inspired by the themes of rebellious play, mindful eating, and the promotion of playful exploration, guided independence, trusted relationships, and family harmony.After testing of prototypes, a final concept was developed and tested by families with children. The final concept called Happi Hanily is a family food play experience that facilitates the reflection of family food values, supports mindful eating, and creates an atmosphere that fosters harmony among family members—all of which promote the development of healthy eating behaviour for the family over time. The design has three elements, the digital Food Finder which is an online recipe platform, the Spill Supporters which are customized napkins, and the Wackey Wavey Wheel of food which is the central serving and eating dish.The final concept was tested with three families using the qualitative methods of observation, questionnaires, and interviews. During testing it was found that the design facilitated a harmonious dinner experience with the qualities of playful exploration, guided independence, and trusted relationships being enhanced. Due to the timeframe of the project it was difficult to measure whether families were able to develop a healthier relationship with food. However, based on parental feedback it appears that children are more engaged while eating with the Happi Hanily and that this product is something they would adopt as a ritual. The design facilitates a more relaxed and stress-free dining experience which is important when introducing new food to children and when helping them to develop a healthier relationship with food.Design for Interactio
Low prevalence of primary biliary cirrhosis in Victoria, Australia. Melbourne Liver Group
No full textA prevalence study of primary biliary cirrhosis was carried out in the state of Victoria, Australia, by means of a mail survey of specialist physicians and a review of hospital records. Eighty four cases were identified, giving a prevalence of 19.1 per million population (95% confidence limits (CI) 15.3, 23.7), which is among the lowest in published reports. The prevalence in the Australian born, at risk population (women over the age of 24) was 51 per million (95% CI 37.5, 67.9). Both these figures are considerably lower than those in populations of similar age distribution in the UK and northern Europe. Since most Victorians are descended from British or European settlers, the low prevalence of primary biliary cirrhosis in this study supports the hypothesis that local environmental factors may be important in the pathogenesis of this disease
Stratification of asthma by lipidomic profiling of induced sputum supernatant.
No full textBACKGROUND
Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features.
OBJECTIVE
To perform a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as healthy controls.
METHODS
Induced sputum supernatant was collected from 211 asthmatic adults and 41 healthy individuals enrolled in the U-BIOPRED study. Sputum lipidomes were characterised by semi-quantitative shotgun mass spectrometry, and clustered using topological data analysis to identify lipid phenotypes.
RESULTS
Shotgun lipidomics of induced sputum supernatant revealed a spectrum of nine molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthmatics and healthy controls, but within the asthmatic population as well. Matching clinical, pathobiological, proteomic and transcriptomic data informed on the underlying disease processes. Sputum lipid phenotypes with higher levels of non-endogenous, cell-derived lipids were associated with significantly worse asthma severity, worse lung function, and elevated granulocyte counts.
CONCLUSION
We propose a novel mechanism of increased lipid loading in the epithelial lining fluid of asthmatics, resulting from the secretion of extracellular vesicles by granulocytic inflammatory cells, which could reduce the ability of pulmonary surfactant to lower surface tension in asthmatic small airways, as well as compromise its role as an immune regulator.
CLINICAL IMPLICATION
Immunomodulation of extracellular vesicle secretion in the lungs may provide a novel therapeutic target for severe asthma
A revised list of diseases of ornamental plants recorded in Western Australia
No full textTHIS list of ornamental diseases constitutes a revision of portion of the census published by Carne (1925) and added to by the same author in 1927.
It contains also records of diseases identified in the period between these earlier publications and June 30, 1961
Membrane lipid composition of bronchial epithelial cells influences antiviral responses during rhinovirus infection
No full textLipids and their mediators have important regulatory functions in many cellular processes, including the innate antiviral response. The aim of this study was to compare the lipid membrane composition of in vitro differentiated primary bronchial epithelial cells (PBECs) with ex vivo bronchial brushings and to establish whether any changes in the lipid membrane composition affect antiviral defence of cells from donors without and with severe asthma. Using mass spectrometry, we showed that the lipid membrane of in vitro differentiated PBECs was deprived of polyunsaturated fatty acids (PUFAs) compared to ex vivo bronchial brushings. Supplementation of the culture medium with arachidonic acid (AA) increased the PUFA-content to more closely match the ex vivo membrane profile. Rhinovirus (RV16) infection of AA-supplemented cultures from healthy donors resulted in significantly reduced viral replication while release of inflammatory mediators and prostaglandin E2 (PGE2) was significantly increased. Indomethacin, an inhibitor of prostaglandin-endoperoxide synthases, suppressed RV16-induced PGE2 release and significantly reduced CXCL-8/IL-8 release from AA-supplemented cultures indicating a link between PGE2 and CXCL8/IL-8 release. In contrast, in AA-supplemented cultures from severe asthmatic donors, viral replication was enhanced whereas PTGS2 expression and PGE2 release were unchanged and CXCL8/IL-8 was significantly reduced in response to RV16 infection.While the PTGS2/COX-2 pathway is initially pro-inflammatory, its downstream products can promote symptom resolution. Thus, reduced PGE2 release during an RV-induced severe asthma exacerbation may lead to prolonged symptoms and slower recovery. Our data highlight the importance of reflecting the in vivo lipid profile in in vitro cell cultures for mechanistic studies
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