3,971 research outputs found
Understanding the impact of chronic obstructive pulmonary disease exacerbations on patient health and quality of life
Exacerbations of chronic obstructive pulmonary disease (COPD) represent a significant clinical problem, and are
associated with decreased lung function, worsening quality of life and decreased physical activity levels, with
even a single exacerbation having detrimental effects. The occurrence of COPD exacerbations can also have a
considerable impact on healthcare costs and mortality rates, with over one-fifth of patients hospitalized for a
COPD exacerbation for the first time dying within one year of discharge. This highlights the need for COPD
exacerbations to be a major focus in clinical practice. Furthermore, the substantial effect that COPD exacerbations can have on patient mental health should not be underestimated. Despite their clinical importance, COPD
exacerbations are poorly recognized and reported by patients, and improving patient understanding and reporting of exacerbations to ensure prompt treatment may minimize their deleterious effects. Renewed focus on
improving current clinical practice with support from evidence-based guidelines is required. This also raises a
challenge to payors, healthcare systems and government policies to do more to tackle the considerable outstanding burden of COPD exacerbations
Molecular dynamics simulations of oscillatory Couette flows with slip boundary conditions
The effect of interfacial slip on steady-state and time-periodic flows of
monatomic liquids is investigated using non-equilibrium molecular dynamics
simulations. The fluid phase is confined between atomically smooth rigid walls,
and the fluid flows are induced by moving one of the walls. In steady shear
flows, the slip length increases almost linearly with shear rate. We found that
the velocity profiles in oscillatory flows are well described by the Stokes
flow solution with the slip length that depends on the local shear rate.
Interestingly, the rate dependence of the slip length obtained in steady shear
flows is recovered when the slip length in oscillatory flows is plotted as a
function of the local shear rate magnitude. For both types of flows, the
friction coefficient at the liquid-solid interface correlates well with the
structure of the first fluid layer near the solid wall.Comment: 31 pages, 11 figure
Individual Eigenvalue Distributions for the Wilson Dirac Operator
We derive the distributions of individual eigenvalues for the Hermitian
Wilson Dirac Operator D5 as well as for real eigenvalues of the Wilson Dirac
Operator DW. The framework we provide is valid in the epsilon regime of chiral
perturbation theory for any number of flavours Nf and for non-zero low energy
constants W6, W7, W8. It is given as a perturbative expansion in terms of the
k-point spectral density correlation functions and integrals thereof, which in
some cases reduces to a Fredholm Pfaffian. For the real eigenvalues of DW at
fixed chirality nu this expansion truncates after at most nu terms for small
lattice spacing "a". Explicit examples for the distribution of the first and
second eigenvalue are given in the microscopic domain as a truncated expansion
of the Fredholm Pfaffian for quenched D5, where all k-point densities are
explicitly known from random matrix theory. For the real eigenvalues of
quenched DW at small "a" we illustrate our method by the finite expansion of
the corresponding Fredholm determinant of size nu.Comment: 20 pages, 5 figures; v2: typos corrected, refs added and discussion
of W6 and W7 extende
The role of mutation rate variation and genetic diversity in the architecture of human disease
Background
We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified.
Results
Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless.
Conclusions
Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease
In silico analyses of metagenomes from human atherosclerotic plaque samples
Background
Through several observational and mechanistic studies, microbial infection is known to promote cardiovascular disease. Direct infection of the vessel wall, along with the cardiovascular risk factors, is hypothesized to play a key role in the atherogenesis by promoting an inflammatory response leading to endothelial dysfunction and generating a proatherogenic and prothrombotic environment ultimately leading to clinical manifestations of cardiovascular disease, e.g., acute myocardial infarction or stroke. There are many reports of microbial DNA isolation and even a few studies of viable microbes isolated from human atherosclerotic vessels. However, high-resolution investigation of microbial infectious agents from human vessels that may contribute to atherosclerosis is very limited. In spite of the progress in recent sequencing technologies, analyzing host-associated metagenomes remain a challenge.
Results
To investigate microbiome diversity within human atherosclerotic tissue samples, we employed high-throughput metagenomic analysis on: (1) atherosclerotic plaques obtained from a group of patients who underwent endarterectomy due to recent transient cerebral ischemia or stroke. (2) Presumed stabile atherosclerotic plaques obtained from autopsy from a control group of patients who all died from causes not related to cardiovascular disease. Our data provides evidence that suggest a wide range of microbial agents in atherosclerotic plaques, and an intriguing new observation that shows these microbiota displayed differences between symptomatic and asymptomatic plaques as judged from the taxonomic profiles in these two groups of patients. Additionally, functional annotations reveal significant differences in basic metabolic and disease pathway signatures between these groups.
Conclusions
We demonstrate the feasibility of novel high-resolution techniques aimed at identification and characterization of microbial genomes in human atherosclerotic tissue samples. Our analysis suggests that distinct groups of microbial agents might play different roles during the development of atherosclerotic plaques. These findings may serve as a reference point for future studies in this area of research
Albumin-based cancer therapeutics for intraperitoneal drug delivery : a review
Albumin is a remarkable carrier protein with multiple cellular receptor and ligand binding sites, which are able to bind and transport numerous endogenous and exogenous compounds. The development of albumin-bound drugs is gaining increased importance in the targeted delivery of cancer therapy. Intraperitoneal (IP) drug delivery represents an attractive strategy for the local treatment of peritoneal metastasis (PM). PM is characterized by the presence of widespread metastatic tumor nodules on the peritoneum, mostly originating from gastro-intestinal or gynaecological cancers. Albumin as a carrier for chemotherapy holds considerable promise for IP delivery in patients with PM. Data from recent (pre)clinical trials suggest that IP albumin-bound chemotherapy may result in superior efficacy in the treatment of PM compared to standard chemotherapy formulations. Here, we review the evidence on albumin-bound chemotherapy with a focus on IP administration and its efficacy in PM
The population of close double white dwarfs in the Galaxy
We present a new model for the Galactic population of close double white
dwarfs. The model accounts for the suggestion of the avoidance of a substantial
spiral-in during mass transfer between a giant and a main-sequence star of
comparable mass and for detailed cooling models. It agrees well with the
observations of the local sample of white dwarfs if the initial binary fraction
is close to 50% and an ad hoc assumption is made that white dwarfs with mass
less than about 0.3 solar mass cool faster than the models suggest. About 1000
white dwarfs brighter than V=15 have to be surveyed for detection of a pair
which has total mass greater than the Chandrasekhar mass and will merge within
10 Gyr.Comment: 15 pages, 7 figures, to appear in Proc. ``The influence of binaries
on stellar population studies'', Brussels, August 2000 (Kluwer, D. Vanbeveren
ed.
A consistent picture for large penguins in D -> pi+ pi-, K+ K-
A long-standing puzzle in charm physics is the large difference between the
D0 -> K+ K- and D0 -> pi+ pi- decay rates. Recently, the LHCb and CDF
collaborations reported a surprisingly large difference between the direct CP
asymmetries, Delta A_CP, in these two modes. We show that the two puzzles are
naturally related in the Standard Model via s- and d-quark "penguin
contractions". Their sum gives rise to Delta A_CP, while their difference
contributes to the two branching ratios with opposite sign. Assuming nominal
SU(3) breaking, a U-spin fit to the D0 -> K+ pi-, pi+ K-, pi+ pi-, K+ K- decay
rates yields large penguin contractions that naturally explain Delta A_CP.
Expectations for the individual CP asymmetries are also discussed.Comment: 24 pages, 8 figure
Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-activated receptor-α
<p>Abstract</p> <p>Background</p> <p>In addition to cytotoxic mechanisms directly impacting neurons, β-amyloid (Aβ)-induced glial activation also promotes release of proinflammatory molecules that may self-perpetuate reactive gliosis and damage neighbouring neurons, thus amplifying neuropathological lesions occurring in Alzheimer's disease (AD). Palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory, analgesic, antiepileptic and neuroprotective effects. PEA is a lipid messenger isolated from mammalian and vegetable tissues that mimics several endocannabinoid-driven actions, even though it does not bind to cannabinoid receptors. Some of its pharmacological properties are considered to be dependent on the expression of peroxisome proliferator-activated receptors-α (PPARα).</p> <p>Findings</p> <p>In the present study, we evaluated the effect of PEA on astrocyte activation and neuronal loss in models of Aβ neurotoxicity. To this purpose, primary rat mixed neuroglial co-cultures and organotypic hippocampal slices were challenged with Aβ<sub>1-42 </sub>and treated with PEA in the presence or absence of MK886 or GW9662, which are selective PPARα and PPARγ antagonists, respectively. The results indicate that PEA is able to blunt Aβ-induced astrocyte activation and, subsequently, to improve neuronal survival through selective PPARα activation. The data from organotypic cultures confirm that PEA anti-inflammatory properties implicate PPARα mediation and reveal that the reduction of reactive gliosis subsequently induces a marked rebound neuroprotective effect on neurons.</p> <p>Conclusions</p> <p>In line with our previous observations, the results of this study show that PEA treatment results in decreased numbers of infiltrating astrocytes during Aβ challenge, resulting in significant neuroprotection. PEA could thus represent a promising pharmacological tool because it is able to reduce Aβ-evoked neuroinflammation and attenuate its neurodegenerative consequences.</p
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