123 research outputs found
Family-centred care in cystic fibrosis: a pilot study in North Queensland, Australia
Aims: The aims were to: (i) examine perceptions of family-centred care of parents of children with cystic fibrosis and healthcare professionals who care for them; (ii) test design and tools in a regional population.
Design: Quantitative pilot study of existing questionnaire.
Methods: The methods involved were comparative, cross-sectional survey of parents of children with cystic fibrosis and health staff in North Queensland, using âPerceptions of Family Centered Care â Parentâ and âPerceptions of Family Centered Care â Staffâ questionnaires; and descriptive study of tools.
Results: Eighteen staff, 14 parents (78%, 61%); using MannâWhitney U, showed no significant differences in scores in categories: âsupportâ ârespectâ, âcollaborationâ. Comments about suitability of questionnaires varied, but were largely positive
Condensation of the plasma membrane at the site of T lymphocyte activation
After activation, T lymphocytes restructure their cell surface to form membrane domains at T cell receptor (TCR)âsignaling foci and immunological synapses (ISs). To address whether these rearrangements involve alteration in the structure of the plasma membrane bilayer, we used the fluorescent probe Laurdan to visualize its lipid order. We observed a condensation of the plasma membrane at TCR activation sites. The formation of ordered domains depends on the presence of the transmembrane protein linker for the activation of T cells and Src kinase activity. Moreover, these ordered domains are stabilized by the actin cytoskeleton. Membrane condensation occurs upon TCR stimulation alone but is prolonged by CD28 costimulation with TCR. In ISs, which are formed by conjugates of TCR transgenic T lymphocytes and cognate antigen-presenting cells, similar condensed membrane phases form first in central regions and later at the periphery of synapses. The formation of condensed membrane domains at T cell activation sites biophysically reflects membrane raft accumulation, which has potential implications for signaling at ISs
The Sydney Playground Project: popping the bubblewrap - unleashing the power of play: a cluster randomized controlled trial of a primary school playground-based intervention aiming to increase children\u27s physical activity and social skills
Background In the Westernised world, numerous children are overweight and have problems with bullying and mental health. One of the underlying causes for all three is postulated to be a decrease in outdoor free play. The aim of the Sydney Playground Project is to demonstrate the effectiveness of two simple interventions aimed to increase children\u27s physical activity and social skills. Methods/Design This study protocol describes the design of a 3-year cluster randomised controlled trial (CRCT), in which schools are the clusters. The study consists of a 13-week intervention and 1 week each of pre-and post-testing. We are recruiting 12 schools (6 control; 6 intervention), with 18 randomly chosen participants aged 5 to 7 years in each school. The two intervention strategies are: (1) Child-based intervention: Unstructured materials with no obvious play value introduced to the playground; and (2) Adult-based intervention: Risk reframing sessions held with parents and teachers with the aim of exploring the benefits of allowing children to engage in activities with uncertain outcomes. The primary outcome of the study, physical activity as measured by accelerometer counts, is assessed at baseline and post-intervention. Additional assessments include social skills and interactions, self-concept, after school time use and anthropometric data. Qualitative data (i.e., transcriptions of audio recordings from the risk reframing sessions and of interviews with selected teacher and parent volunteers) are analysed to understand their perceptions of risk in play. The control schools have recess as usual. In addition to outcome evaluation, regular process evaluation sessions are held to monitor fidelity to the treatment. Discussion These simple interventions, which could be adopted in every primary school, have the potential of initiating a self-sustaining cycle of prevention for childhood obesity, bullying and mental ill health
Caveolin-1-mediated apolipoprotein A-I membrane binding sites are not required for cholesterol efflux
Caveolin-1 (Cav1), a structural protein required for the formation of invaginated membrane domains known as caveolae, has been implicated in cholesterol trafficking and homeostasis. Here we investigated the contribution of Cav1 to apolipoprotein A-I (apoA-I) cell surface binding and intracellular processing using mouse embryonic fibroblasts (MEFs) derived from wild type (WT) or Cav1-deficient (Cav1â/â) animals. We found that cells expressing Cav1 have 2.6-fold more apoA-I binding sites than Cav1â/â cells although these additional binding sites are not associated with detergent-free lipid rafts. Further, Cav1-mediated binding targets apoA-I for internalization and degradation and these processes are not correlated to cholesterol efflux. Despite lower apoA-I binding, cholesterol efflux from Cav1â/â MEFs is 1.7-fold higher than from WT MEFs. Stimulation of ABCA1 expression with an LXR agonist enhances cholesterol efflux from both WT and Cav1â/â cells without increasing apoA-I surface binding or affecting apoA-I processing. Our results indicate that there are at least two independent lipid binding sites for apoA-I; Cav1-mediated apoA-I surface binding and uptake is not linked to cholesterol efflux, indicating that membrane domains other than caveolae regulate ABCA1-mediated cholesterol efflux
Sphingomyelin phosphodiesterase Acid-like 3A (SMPDL3A) is a novel nucleotide phosphodiesterase regulated by cholesterol in human macrophages
Cholesterol-loaded foam cell macrophages are prominent in atherosclerotic lesions and play complex roles in both inflammatory signaling and lipid metabolism, which are underpinned by large scale reprogramming of gene expression. We performed a microarray study of primary human macrophages that showed that transcription of the sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) gene is up-regulated after cholesterol loading. SMPDL3A protein expression in and secretion from primary macrophages are stimulated by cholesterol loading, liver X receptor ligands, and cyclic AMP, and N-glycosylated SMPDL3A protein is detectable in circulating blood. We demonstrate for the first time that SMPDL3A is a functional phosphodiesterase with an acidic pH optimum. We provide evidence that SMPDL3A is not an acid sphingomyelinase but unexpectedly is active against nucleotide diphosphate and triphosphate substrates at acidic and neutral pH. SMPDL3A is a major source of nucleotide phosphodiesterase activity secreted by liver X receptor-stimulated human macrophages. Extracellular nucleotides such as ATP may activate pro-inflammatory responses in immune cells. Increased expression and secretion of SMPDL3A by cholesterol-loaded macrophage foam cells in lesions may decrease local concentrations of pro-inflammatory nucleotides and potentially represent a novel anti-inflammatory axis linking lipid metabolism with purinergic signaling in atherosclerosis
2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients With Advanced Heart Failure and Cardiac Transplant)
Since the 1995 publication of its Core Cardiovascular Training Statement (COCATS),1 the American College of Cardiology (ACC) has played a central role in defining the knowledge, experiences, skills, and behaviors expected of all clinical cardiologists upon completion of training. Subsequent updates have incorporated major advances and revisionsâboth in content and structureâincluding, most recently,
Role of ABCG1 and ABCA1 in regulation of neuronal cholesterol efflux to apolipoprotein E discs and suppression of amyloid-β peptide generation
Maintenance of an adequate supply of cholesterol is important for neuronal function, whereas excess cholesterol promotes amyloid precursor protein (APP) cleavage generating toxic amyloid-β (Aβ) peptides. To gain insights into the pathways that regulate neuronal cholesterol level, we investigated the potential for reconstituted apolipoprotein E (apoE) discs, resembling nascent lipoprotein complexes in the central nervous system, to stimulate neuronal [3H]cholesterol efflux. ApoE discs potently accelerated cholesterol efflux from primary human neurons and cell lines. The process was saturable (17.5 Îźg of apoE/ml) and was not influenced by APOE genotype. High performance liquid chromatography analysis of cholesterol and cholesterol metabolites effluxed from neurons indicated that <25% of the released cholesterol was modified to polar products (e.g. 24-hydroxycholesterol) that diffuse from neuronal membranes. Thus, most cholesterol (âź75%) appeared to be effluxed from neurons in a native state via a transporter pathway. ATP-binding cassette transporters ABCA1, ABCA2, and ABCG1 were detected in neurons and neuroblastoma cell lines and expression of these cDNAs revealed that ABCA1 and ABCG1 stimulated cholesterol efflux to apoE discs. In addition, ABCA1 and ABCG1 expression in Chinese hamster ovary cells that stably express human APP significantly reduced Aβ generation, whereas ABCA2 did not modulate either cholesterol efflux or Aβ generation. These data indicate that ABCA1 and ABCG1 play a significant role in the regulation of neuronal cholesterol efflux to apoE discs and in suppression of APP processing to generate Aβ peptides
TRAIL-Expressing Monocyte/Macrophages Are Critical for Reducing Inflammation and Atherosclerosis.
Circulating tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) levels are reduced in patients with cardiovascular disease, and TRAIL gene deletion in mice exacerbates atherosclerosis and inflammation. How TRAIL protects against atherosclerosis and why levels are reduced in disease is unknown. Here, multiple strategies were used to identify the protective source of TRAIL and its mechanism(s) of action. Samples from patients with coronary artery disease and bone-marrow transplantation experiments in mice lacking TRAIL revealed monocytes/macrophages as the main protective source. Accordingly, deletion of TRAIL caused a more inflammatory macrophage with reduced migration, displaying impaired reverse cholesterol efflux and efferocytosis. Furthermore, interleukin (IL)-18, commonly increased in plasma of patients with cardiovascular disease, negatively regulated TRAIL transcription and gene expression, revealing an IL-18-TRAIL axis. These findings demonstrate that TRAIL is protective of atherosclerosis by modulating monocyte/macrophage phenotype and function. Manipulating TRAIL levels in these cells highlights a different therapeutic avenue in the treatment of cardiovascular disease
Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease
Peer reviewe
Vitamin D supplementation in adolescent female ballet dancers and gymnasts in a 12 month randomised controlled trial in Auckland, New Zealand : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Nutrition and Dietetics at Massey University, Albany, New Zealand
Aim:
To
examine
the
effects
of
vitamin
D
supplementation
on
the
bone
health
of
female
adolescent
ballet
dancers
and
gymnasts.
Method:
Adolescent
female
ballet
dancers
and
gymnasts
from
Auckland,
New
Zealand
were
recruited
to
a
12
month
randomised
double-Ââblind
trial.
Participants
were
supplemented
with
cholecalciferol
50,000
IU
per
month
or
a
placebo.
At
baseline
detailed
dietary
intake
was
collected
by
a
four
day
food
record;
at
baseline
and
12
months
bone
mineral
density
(BMD)
and
content
were
recorded
by
DXA
as
well
as
bone-Ââfree,
fat-Ââfree,
lean
body
mass,
percentage
body
fat,
height
and
weight.
At
baseline,
six
months
and
12
months
serum
markers
for
vitamin
D
(oestradiol
and
parathyroid
hormone)
were
collected.
Results:
A
total
of
61
adolescent
girls
were
recruited
at
baseline,
BMD
and
content
by
DXA
was
completed
in
45
girls
and
41
provided
vitamin
D
serum
samples.
Serum
vitamin
D
concentration
was
recorded
for
41
female
ballet
dancers
and
gymnasts
aged
12
to
18
years
was
72
nmol/L
and
remained
adequate
(>50
nmol/L)
in
both
intervention
and
control
groups
for
the
12
month
duration.
There
was
no
significant
difference
between
intervention
and
control
groups
in
bone
mineral
density
and
content
at
any
bone
site
at
12
months.
The
significant
predictors
of
increased
bone
mineral
density
at
baseline
were
older
age
(P=0.002)
higher
bone-Ââfree,
fat-Ââfree,
lean
body
mass
(P=0.001)
and
higher
calcium
intake
(P=0.005).
For
higher
bone
mineral
content
the
significant
predictors
at
baseline
were
older
age
(P=0.01)
and
higher
bone-Ââ
free,
fat-Ââfree,
lean
body
mass
(P=0.001).
In
all
participants
(n=48)
bone
mineral
density
and
content
increased
significantly
at
12
months
(total
body
BMD
and
content,
areal
BMD,
total
hip
BMD
and
content,
femoral
neck
BMD
and
content
and
lumbar
spine
BMD
and
content).
II
Discussion:
More
than
adequate
baseline
serum
vitamin
D
levels
in
this
adolescent
group
may
explain
the
lack
of
significant
difference
in
any
of
the
bone
measures
between
intervention
and
control
groups.
As
the
age
range
of
the
adolescent
girls
varied
markedly
and
older
age
predicted
both
an
increase
in
BMD
and
content,
it
is
likely
that
there
was
also
bone
accrual
due
to
growth.
The
nil
effect
of
vitamin
D
supplementation
on
bone
measures
was
also
limited
by
the
small
sample
size.
Conclusion:
In
this
study
vitamin
D
supplementation
had
no
effect
on
the
bone
mineral
density
and
content
of
female
adolescent
ballet
dancers
and
gymnasts.
Further
investigations
are
needed
to
examine
vitamin
D
supplementation
on
bone
measures
in
a
large
group
of
adolescent
girls
- âŚ