1,197 research outputs found
Tip–sample interactions: Extraction of single molecular pair potentials from force curves
This article describes a method for extracting the true tip–sample potential from an experimental force curve in atomic force microscopy. This potential is not the negative integral of the force curve. Rather, the potential is a more complicated function of the force curve and cantilever spring constant. If information about the shape of the tip is known, a decorrelation may be performed to extract molecular pair potentials from the total tip–sample potential. Applications and limitations of this method are discussed
NCBO Ontology Recommender 2.0: An Enhanced Approach for Biomedical Ontology Recommendation
Biomedical researchers use ontologies to annotate their data with ontology
terms, enabling better data integration and interoperability. However, the
number, variety and complexity of current biomedical ontologies make it
cumbersome for researchers to determine which ones to reuse for their specific
needs. To overcome this problem, in 2010 the National Center for Biomedical
Ontology (NCBO) released the Ontology Recommender, which is a service that
receives a biomedical text corpus or a list of keywords and suggests ontologies
appropriate for referencing the indicated terms. We developed a new version of
the NCBO Ontology Recommender. Called Ontology Recommender 2.0, it uses a new
recommendation approach that evaluates the relevance of an ontology to
biomedical text data according to four criteria: (1) the extent to which the
ontology covers the input data; (2) the acceptance of the ontology in the
biomedical community; (3) the level of detail of the ontology classes that
cover the input data; and (4) the specialization of the ontology to the domain
of the input data. Our evaluation shows that the enhanced recommender provides
higher quality suggestions than the original approach, providing better
coverage of the input data, more detailed information about their concepts,
increased specialization for the domain of the input data, and greater
acceptance and use in the community. In addition, it provides users with more
explanatory information, along with suggestions of not only individual
ontologies but also groups of ontologies. It also can be customized to fit the
needs of different scenarios. Ontology Recommender 2.0 combines the strengths
of its predecessor with a range of adjustments and new features that improve
its reliability and usefulness. Ontology Recommender 2.0 recommends over 500
biomedical ontologies from the NCBO BioPortal platform, where it is openly
available.Comment: 29 pages, 8 figures, 11 table
Poor uptake of reproductive health screening services by female renal transplant recipients.
Women with functioning renal transplants are a high-risk group for de novo malignancies and other gynaecological
health problems. The objective of this study was to assess patients awareness of gynaecological issues, and to assess
uptake of cervical and breast cancer screening services. A structured questionnaire on family planning, menopausal
issues and knowledge/use of cervical and breast cancer screening was administered to 64 female renal transplant
recipients. 58 (91%) responded to the questionnaire. Mean age at first transplantation was 35 years (range 11 - 69).
84% were aware as to why they should have regular cervical smears. 15 (26%) had, however, never had a smear and only 9
(16%) were having yearly smears. 12 of 28 postmenopausal women entered the menopause under the age of 41 years, but
only 5 of these had received Hormone Replacement Therapy. Breast self examination is practiced by 71%, but only 26%
have had mammograms. These figures suggest that female renal transplant patients are not adequately screened for
cervical and breast cancer. The results also indicate a need for further education regarding family planning issues
and menopausal health concerns. We conclude that formal gynaecological review should be routinely available for women with renal transplants
Systolic blood pressure reduction during the first 24 h in acute heart failure admission: friend or foe?
Aims:
Changes in systolic blood pressure (SBP) during an admission for acute heart failure (AHF), especially those leading to hypotension, have been suggested to increase the risk for adverse outcomes.
Methods and results:
We analysed associations of SBP decrease during the first 24 h from randomization with serum creatinine changes at the last time-point available (72 h), using linear regression, and with 30- and 180-day outcomes, using Cox regression, in 1257 patients in the VERITAS study. After multivariable adjustment for baseline SBP, greater SBP decrease at 24 h from randomization was associated with greater creatinine increase at 72 h and greater risk for 30-day all-cause death, worsening heart failure (HF) or HF readmission. The hazard ratio (HR) for each 1 mmHg decrease in SBP at 24 h for 30-day death, worsening HF or HF rehospitalization was 1.01 [95% confidence interval (CI) 1.00–1.02; P = 0.021]. Similarly, the HR for each 1 mmHg decrease in SBP at 24 h for 180-day all-cause mortality was 1.01 (95% CI 1.00–1.03; P = 0.038). The associations between SBP decrease and outcomes did not differ by tezosentan treatment group, although tezosentan treatment was associated with a greater SBP decrease at 24 h.
Conclusions:
In the current post hoc analysis, SBP decrease during the first 24 h was associated with increased renal impairment and adverse outcomes at 30 and 180 days. Caution, with special attention to blood pressure monitoring, should be exercised when vasodilating agents are given to AHF patients
Predictors and associations with outcomes of length of hospital stay in patients with acute heart failure: results from VERITAS
Background:
The length of hospital stay (LOS) is important in patients admitted for acute heart failure (AHF) because it prolongs an unpleasant experience for the patients and adds substantially to health care costs.
Methods and Results:
We examined the association between LOS and baseline characteristics, 10-day post-discharge HF readmission, and 90-day post-discharge mortality in 1347 patients with AHF enrolled in the VERITAS program. Longer LOS was associated with greater HF severity and disease burden at baseline; however, most of the variability of LOS could not be explained by these factors. LOS was associated with a higher HF risk of both HF readmission (odds ratio for 1-day increase: 1.08; 95% confidence interval [CI] 1.01–1.16; P = .019) and 90-day mortality (hazard ratio for 1-day increase: 1.05; 95% CI 1.02–1.07; P < .001), although these associations are partially explained by concurrent end-organ damage and worsening heart failure during the first days of admission.
Conclusions:
In patients who have been admitted for AHF, longer length of hospital stay is associated with a higher rate of short-term mortality.
Clinical Trial Registration:
VERITAS-1 and -2: Clinicaltrials.gov identifiers NCT00525707 and NCT00524433
Rethinking the bile acid/gut microbiome axis in cancer
Dietary factors, probiotic agents, aging and antibiotics/medicines impact on gut microbiome composition leading to disturbances in localised microbial populations. The impact can be profound and underlies a plethora of human disorders, including the focus of this review; cancer. Compromised microbiome populations can alter bile acid signalling and produce distinct pathophysiological bile acid profiles. These in turn have been associated with cancer development and progression. Exposure to high levels of bile acids, combined with localised molecular/genome instability leads to the acquisition of bile mediated neoplastic alterations, generating apoptotic resistant proliferation phenotypes. However, in recent years, several studies have emerged advocating the therapeutic benefits of bile acid signalling in suppressing molecular and phenotypic hallmarks of cancer progression. These studies suggest that in some instances, bile acids may reduce cancer phenotypic effects, thereby limiting metastatic potential. In this review, we contextualise the current state of the art to propose that the bile acid/gut microbiome axis can influence cancer progression to the extent that classical in vitro cancer hallmarks of malignancy (cell invasion, cell migration, clonogenicity, and cell adhesion) are significantly reduced. We readily acknowledge the existence of a bile acid/gut microbiome axis in cancer initiation, however, in light of recent advances, we focus exclusively on the role of bile acids as potentially beneficial molecules in suppressing cancer progression. Finally, we theorise that suppressing aggressive malignant phenotypes through bile acid/gut microbiome axis modulation could uncover new and innovative disease management strategies for managing cancers in vulnerable cohort
A network analysis to compare biomarker profiles in patients with and without diabetes mellitus in acute heart failure
Aims:
It is unclear whether distinct pathophysiological processes are present among patients with acute heart failure (AHF), with and without diabetes. Network analysis of biomarkers may identify correlative associations that reflect different pathophysiological pathways.
Methods and results:
We analysed a panel of 48 circulating biomarkers measured within 24 h of admission for AHF in a subset of patients enrolled in the PROTECT trial. In patients with and without diabetes, we performed a network analysis to identify correlations between measured biomarkers. Compared with patients without diabetes (n = 1111), those with diabetes (n = 922) had a higher prevalence of ischaemic heart disease and traditional coronary risk factors. After multivariable adjustment, patients with and without diabetes had significantly different levels of biomarkers across a spectrum of pathophysiological domains, including inflammation (TNFR-1a, periostin), cardiomyocyte stretch (BNP), angiogenesis (VEGFR, angiogenin), and renal function (NGAL, KIM-1) (adjusted P-value <0.05). Among patients with diabetes, network analysis revealed that periostin strongly clustered with C-reactive protein and interleukin-6. Furthermore, renal markers (creatinine and NGAL) closely associated with potassium and glucose. These findings were not seen among patients without diabetes.
Conclusion:
Patients with AHF and diabetes, compared with those without diabetes, have distinct biomarker profiles. Network analysis suggests that cardiac remodelling, inflammation, and fibrosis are closely associated with each other in patients with diabetes. Furthermore, potassium levels may be sensitive to changes in renal function as reflected by the strong renal–potassium–glucose correlation. These findings were not seen among patients without diabetes and may suggest distinct pathophysiological processes among AHF patients with diabetes
Rolofylline, an adenosine A1−receptor antagonist, in acute heart failure
Background:
Worsening renal function, which is associated with adverse outcomes, often develops
in patients with acute heart failure. Experimental and clinical studies suggest that
counterregulatory responses mediated by adenosine may be involved. We tested the
hypothesis that the use of rolofylline, an adenosine A1−receptor antagonist, would
improve dyspnea, reduce the risk of worsening renal function, and lead to a more
favorable clinical course in patients with acute heart failure.
Methods:
We conducted a multicenter, double-blind, placebo-controlled trial involving patients
hospitalized for acute heart failure with impaired renal function. Within 24 hours
after presentation, 2033 patients were randomly assigned, in a 2:1 ratio, to receive
daily intravenous rolofylline (30 mg) or placebo for up to 3 days. The primary end
point was treatment success, treatment failure, or no change in the patient’s clinical
condition; this end point was defined according to survival, heart-failure status,
and changes in renal function. Secondary end points were the post-treatment development
of persistent renal impairment and the 60-day rate of death or readmission
for cardiovascular or renal causes.
Results:
Rolofylline, as compared with placebo, did not provide a benefit with respect to the
primary end point (odds ratio, 0.92; 95% confidence interval, 0.78 to 1.09; P=0.35).
Persistent renal impairment developed in 15.0% of patients in the rolofylline group
and in 13.7% of patients in the placebo group (P=0.44). By 60 days, death or readmission
for cardiovascular or renal causes had occurred in similar proportions of patients
assigned to rolofylline and placebo (30.7% and 31.9%, respectively; P=0.86).
Adverse-event rates were similar overall; however, only patients in the rolofylline
group had seizures, a known potential adverse effect of A1-receptor antagonists.
Conclusions:
Rolofylline did not have a favorable effect with respect to the primary clinical composite
end point, nor did it improve renal function or 60-day outcomes. It does not
show promise in the treatment of acute heart failure with renal dysfunction. (Funded
by NovaCardia, a subsidiary of Merck; ClinicalTrials.gov numbers, NCT00328692
and NCT00354458.
- …