578 research outputs found

    An updated interactive database for 1692 genetic variants in coagulation Factor IX provides detailed insights into haemophilia B

    Get PDF
    BACKGROUND: Genetic variants in coagulation factor IX (FIX) are associated with haemophilia B, a rare bleeding disease. F9 variants are widespread across the gene and were summarised in our FIX variant database introduced in 2013. OBJECTIVE: We rationalise the molecular basis for 598 new F9 variants and 1645 new clinical cases, making a total of 1692 F9 variants and 5358 related patient cases. METHODS: New F9 variants were identified from publications and on-line resources, and compiled into a MySQL database for comparison with the human FIXa protein structure. RESULTS: The new total of 1692 F9 variants correspond to 406 (88%) of the 461 FIX residues and now include 70 additional residues. These comprise 945 unique point variants, 281 deletions, 352 polymorphisms, 63 insertions, and 51 others. Most FIX variants were point variants, although their proportion (56%) has reduced compared to 2013 (73%), while the proportion of polymorphisms has increased from 5% to 21%.The 764 unique mild severity variants in the mature protein with known phenotypes include 74 (9.7%) quantitative type I variants and 116 (15.2%) predominantly qualitative type II variants. The remaining 574 variants types are unspecified. Inhibitors are associated with 152 haemophilia B cases out of 5358 patients (2.8%), an increase of 93 from the previous database. CONCLUSION: The even distribution of the F9 variants revealed few mutational hotspots, and most variants were associated with small perturbations in the FIX protein structure. The updated database will assist clinicians and researchers in assessing treatments for haemophilia B patients

    The effectiveness of a sustained nurse home visiting intervention for Aboriginal infants compared with non-Aboriginal infants and with Aboriginal infants receiving usual child health care : a quasi-experimental trial : the Bulundidi Gudaga study

    Get PDF
    Background: In Australia there is commitment to developing interventions that will 'Close the Gap' between the health and welfare of Indigenous and non-Indigenous Australians and recognition that early childhood interventions offer the greatest potential for long term change. Nurse led sustained home visiting programs are considered an effective way to deliver a health and parenting service, however there is little international or Australian evidence that demonstrates the effectiveness of these programs for Aboriginal infants. This protocol describes the Bulundidi Gudaga Study, a quasi-experimental design, comparing three cohorts of families from the Macarthur region in south western Sydney to explore the effectiveness of the Maternal Early Childhood Sustained Home-visiting (MECSH) program for Aboriginal families. Methods: Mothers were recruited when booking into the local hospital for perinatal care and families are followed up until child is age 4 years. Participants are from three distinct cohorts: Aboriginal MECSH intervention cohort (Group A), Non-Aboriginal MECSH intervention cohort (Group B) and Aboriginal non-intervention cohort (Group C). Eligible mothers were those identified as at risk during the Safe Start assessment conducted by antenatal clinic midwives. Mothers in Group A were eligible if they were pregnant with an Aboriginal infant. Mothers in Group B were eligible if they were pregnant with a non-Aboriginal infant. Mothers in Group C are part of the Gudaga descriptive cohort study and were recruited between October 2005 and May 2007. The difference in duration of breastfeeding, child body mass index, and child development outcomes at 18 months and 4 years of age will be measured as primary outcomes. We will also evaluate the intervention effect on secondary measures including: child dental health; the way the program is received; patterns of child health and illness; patterns of maternal health, health knowledge and behaviours; family and environmental conditions; and service usage for mothers and families. Discussion: Involving local Aboriginal research and intervention staff and investing in established relationships between the research team and the local Aboriginal community is enabling this study to generate evidence regarding the effectiveness of interventions that are feasible to implement and sustainable in the context of Aboriginal communities and local service systems. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12616001721493 Registered 14 Dec 2016. Retrospectively registered

    Connecting Online Graduate Students to the University Community

    Get PDF
    The purpose of this study was to understand how to facilitate a sense of belonging among online graduate students. Sense of community theory was the basis for examining students’ desires to be a part of a community and feel connected to the institution. Findings from a survey using the Sense of Community Index 2 (SCI-2) of online graduate students provided insight into the sense of community, the importance of belonging to a community, and activities that could strengthen their connection with the institution. Overall students showed a slightly stronger sense of belonging to their program than to the institution. Students were also asked how they prefer to connect to others in the community with mentoring and inperson social events being the most requested

    An epigenome-wide association study of child appetitive traits and DNA methylation

    Get PDF
    The etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4–5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors.</p

    Foliar water uptake via cork warts in mangroves of the Sonneratia genus

    Get PDF
    Foliar water uptake (FWU) occurs in plants of diverse ecosystems; however, the diversity of pathways and their associated FWU kinetics remain poorly resolved. We characterized a novel FWU pathway in two mangrove species of the Sonneratia genus, S. alba and S. caseolaris. Further, we assessed the influence of leaf wetting duration, wet-dry seasonality and leaf dehydration on leaf conductance to surface water (Ksurf ). The symplastic tracer dye, disodium fluorescein, revealed living cells subtending and encircling leaf epidermal structures known as cork warts as a pathway of FWU entry into the leaf. Rehydration kinetics experiments revealed a novel mode of FWU, with slow and steady rates of water uptake persistent over a duration of 12 h. Ksurf increased with longer durations of leaf wetting and was greater in leaves with more negative water potentials at the initiation of leaf wetting. Ksurf declined by 68% between wet and dry seasons. Our results suggest that FWU via cork warts in Sonneratia sp. may be rate limited and under active regulation. We conclude that FWU pathways in halophytes may require ion exclusion to avoid uptake of salt when inundated, paralleling the capacity of halophyte roots for ion selectivity during water acquisition. This article is protected by copyright. All rights reserved.The project was funded by the Australian Research Council Discovery Grant Projects DP150104437 and DP180102969 awarded to MCB. TIF was supported by the Becas Chile PhD scholarship program granted by ANID. CB, HAB and RJH were supported by Australian Government Research Training Program (RTP) Scholarships. HIH was supported by an NSF Graduate Research Fellowship and a NSF GROW Fellowship. OB was supported by Australian Research Council Discovery Grant DP17010409

    Detection of SARS-CoV-2-specific mucosal antibodies in saliva following concomitant COVID-19 and influenza vaccination in the ComFluCOV trial

    Get PDF
    The ComFluCOV trial randomized 679 participants to receive an age-appropriate influenza vaccine, or placebo, alongside their second COVID-19 vaccine. Concomitant administration was shown to be safe, and to preserve systemic immune responses to both vaccines. Here we report on a secondary outcome of the trial investigating SARS-CoV-2-specific mucosal antibody responses. Anti-spike IgG and IgA levels in saliva were measured with in-house ELISAs. Concomitant administration of an influenza vaccine did not affect salivary anti-spike IgG positivity rates to Pfizer/BioNTech BNT162b2 (99.1 cf. 95.6%), or AstraZeneca ChAdOx1 (67.8% cf. 64.9%), at 3-weeks post-vaccination relative to placebo. Furthermore, saliva IgG positively correlated with serum titres highlighting the potential utility of saliva for assessing differences in immunogenicity in future vaccine studies. Mucosal IgA was not detected in response to either COVID-19 vaccine, reinforcing the need for novel vaccines capable of inducing sterilising immunity or otherwise reducing transmission. The trial is registered as ISRCTN 14391248

    Effect of 28 days of creatine ingestion on muscle metabolism and performance of a simulated cycling road race

    Get PDF
    <p>Abstract</p> <p>Purpose</p> <p>The effects of creatine supplementation on muscle metabolism and exercise performance during a simulated endurance road race was investigated.</p> <p>Methods</p> <p>Twelve adult male (27.3 ± 1.0 yr, 178.6 ± 1.4 cm, 78.0 ± 2.5 kg, 8.9 ± 1.1 %fat) endurance-trained (53.3 ± 2.0 ml* kg<sup>-1</sup>* min<sup>-1</sup>, cycling ~160 km/wk) cyclists completed a simulated road race on a cycle ergometer (Lode), consisting of a two-hour cycling bout at 60% of peak aerobic capacity (VO<sub>2peak</sub>) with three 10-second sprints performed at 110% VO<sub>2 peak </sub>every 15 minutes. Cyclists completed the 2-hr cycling bout before and after dietary creatine monohydrate or placebo supplementation (3 g/day for 28 days). Muscle biopsies were taken at rest and five minutes before the end of the two-hour ride.</p> <p>Results</p> <p>There was a 24.5 ± 10.0% increase in resting muscle total creatine and 38.4 ± 23.9% increase in muscle creatine phosphate in the creatine group (<it>P </it>< 0.05). Plasma glucose, blood lactate, and respiratory exchange ratio during the 2-hour ride, as well as VO<sub>2 peak</sub>, were not affected by creatine supplementation. Submaximal oxygen consumption near the end of the two-hour ride was decreased by approximately 10% by creatine supplementation (P < 0.05). Changes in plasma volume from pre- to post-supplementation were significantly greater in the creatine group (<sup>+</sup>14.0 ± 6.3%) than the placebo group (<sup>-</sup>10.4 ± 4.4%; <it>P </it>< 0.05) at 90 minutes of exercise. The time of the final sprint to exhaustion at the end of the 2-hour cycling bout was not affected by creatine supplementation (creatine pre, 64.4 ± 13.5s; creatine post, 88.8 ± 24.6s; placebo pre, 69.0 ± 24.8s; placebo post 92.8 ± 31.2s: creatine vs. placebo not significant). Power output for the final sprint was increased by ~33% in both groups (creatine vs. placebo not significant).</p> <p>Conclusions</p> <p>It can be concluded that although creatine supplementation may increase resting muscle total creatine, muscle creatine phosphate, and plasma volume, and may lead to a reduction in oxygen consumption during submaximal exercise, creatine supplementation does not improve sprint performance at the end of endurance cycling exercise.</p

    The role of food selectivity in the association between child autistic traits and constipation

    Get PDF
    Objective: This study examines the association between child autistic traits and constipation symptoms, and explores whether this association is mediated by food selectivity. Method: The sample included participants (N = 2,818) from the population-based birth cohort, Generation R (Rotterdam, the Netherlands). Parents reported their child's autistic traits at 6 years (using the Social Responsiveness Scale), food selectivity at 10 years (using the Stanford Feeding Questionnaire) and the frequency and severity of constipation symptoms they experienced at 10 years (using the ROME III functional constipation diagnostic criteria). Mediation analyses tested mediation through food selectivity in t
    • …
    corecore