453 research outputs found
A novel technique for selective NF-kappa B inhibition in Kupffer cells: contrary effects in fulminant hepatitis and ischaemia-reperfusion.
Background and aims: The transcription factor nuclear
factor kappa B (NF-kB) has risen as a promising target for
anti-inflammatory therapeutics. In the liver, however, NFkB
inhibition mediates both damaging and protective
effects. The outcome is deemed to depend on the liver
cell type addressed. Recent gene knock-out studies
focused on the role of NF-kB in hepatocytes, whereas the
role of NF-kB in Kupffer cells has not yet been
investigated in vivo. Here we present a novel approach,
which may be suitable for clinical application, to
selectively target NF-kB in Kupffer cells and analyse the
effects in experimental models of liver injury.
Methods: NF-kB inhibiting decoy oligodeoxynucleotides
were loaded upon gelatin nanoparticles (D-NPs) and their
in vivo distribution was determined by confocal microscopy.
Liver damage, NF-kB activity, cytokine levels and
apoptotic protein expression were evaluated after
lipopolysaccharide (LPS), D-galactosamine (GalN)/LPS, or
concanavalin A (ConA) challenge and partial warm
ischaemia and subsequent reperfusion, respectively.
Results: D-NPs were selectively taken up by Kupffer cells
and inhibited NF-kB activation. Inhibition of NF-kB in
Kupffer cells improved survival and reduced liver injury
after GalN/LPS as well as after ConA challenge. While
anti-apoptotic protein expression in liver tissue was not
reduced, pro-apoptotic players such as cJun N-terminal
kinase (JNK) were inhibited. In contrast, selective
inhibition of NF-kB augmented reperfusion injury.
Conclusions: NF-kB inhibiting decoy oligodeoxynucleotide-
loaded gelatin nanoparticles is a novel tool to
selectively inhibit NF-kB activation in Kupffer cells in vivo.
Thus, liver injury can be reduced in experimental fulminant
hepatitis, but increased at ischaemia–reperfusion
Investigations on Tetragonally Distorted Sodium Thallide NaTl‐tI8
In-depth investigations of the long-time known Zintl phase NaTl revealed a phase transition of tetragonal NaTl-tI8 [I4(1)/amd; a = 5.2268(9) angstrom, c = 7.539(1) angstrom, V = 205.97(9) angstrom(3)] to Zintl's cubic NaTl-cF16 [Fd3m; a = 7.4697(6) angstrom, V = 416.79(5) angstrom(3)] between 351 and 355 K. This phase transformation was observed for NaTl prepared by two different synthetic routes including Zintl's original procedure. An excess of sodium applied during the synthesis in liquid ammonia also resulted in the formation of NaTl-tI8. DSC measurements suggest a first order phase transition. In addition to in-situ temperature dependent powder X-ray diffraction experiments, DSC measurements and solid-state NMR investigations, we also performed theoretical DOS and band structure calculations for the cubic and tetragonal phase, respectively. The results suggest Na-Tl interactions in the second coordination sphere being responsible for the observed tetragonal distortion of Zintl's cubic NaTl
Velocity and density profiles of granular flow in channels using lattice gas automaton
We have performed two-dimensional lattice-gas-automaton simulations of
granular flow between two parallel planes. We find that the velocity profiles
have non-parabolic distributions while simultaneously the density profiles are
non-uniform. Under non-slip boundary conditions, deviation of velocity profiles
from the parabolic form of newtonian fluids is found to be characterized solely
by ratio of maximal velocity at the center to the average velocity, though the
ratio depends on the model parameters in a complex manner. We also find that
the maximal velocity () at the center is a linear function of the
driving force (g) as with non-zero in
contrast with newtonian fluids. Regarding density profiles, we observe that
densities near the boundaries are higher than those in the center. The width of
higher densities (above the average density) relative to the channel width is a
decreasing function of a variable which scales with the driving force (g),
energy dissipation parameter () and the width of the system (L) as
with exponents and . A phenomenological theory based on a scaling argument is presented to
interpret these findings.Comment: Latex, 15 figures, to appear in PR
PSS37 the Clinical and Economic Burden of Acute Otitis Media: A Large Prospective Observational Cohort Study in Europe
Bounded Languages Meet Cellular Automata with Sparse Communication
Cellular automata are one-dimensional arrays of interconnected interacting
finite automata. We investigate one of the weakest classes, the real-time
one-way cellular automata, and impose an additional restriction on their
inter-cell communication by bounding the number of allowed uses of the links
between cells. Moreover, we consider the devices as acceptors for bounded
languages in order to explore the borderline at which non-trivial decidability
problems of cellular automata classes become decidable. It is shown that even
devices with drastically reduced communication, that is, each two neighboring
cells may communicate only constantly often, accept bounded languages that are
not semilinear. If the number of communications is at least logarithmic in the
length of the input, several problems are undecidable. The same result is
obtained for classes where the total number of communications during a
computation is linearly bounded
Exact Solution of an Evolutionary Model without Ageing
We introduce an age-structured asexual population model containing all the
relevant features of evolutionary ageing theories. Beneficial as well as
deleterious mutations, heredity and arbitrary fecundity are present and managed
by natural selection. An exact solution without ageing is found. We show that
fertility is associated with generalized forms of the Fibonacci sequence, while
mutations and natural selection are merged into an integral equation which is
solved by Fourier series. Average survival probabilities and Malthusian growth
exponents are calculated indicating that the system may exhibit mutational
meltdown. The relevance of the model in the context of fissile reproduction
groups as many protozoa and coelenterates is discussed.Comment: LaTeX file, 15 pages, 2 ps figures, to appear in Phys. Rev.
Prescribing patterns in dementia: a multicentre observational study in a German network of CAM physicians
<p>Abstract</p> <p>Background</p> <p>Dementia is a major and increasing health problem worldwide. This study aims to investigate dementia treatment strategies among physicians specialised in complementary and alternative medicine (CAM) by analysing prescribing patterns and comparing them to current treatment guidelines in Germany.</p> <p>Methods</p> <p>Twenty-two primary care physicians in Germany participated in this prospective, multicentre observational study. Prescriptions and diagnoses were reported for each consecutive patient. Data were included if patients had at least one diagnosis of dementia according to the 10th revision of the International Classification of Diseases during the study period. Multiple logistic regression was used to determine factors associated with a prescription of any anti-dementia drug including <it>Ginkgo biloba</it>.</p> <p>Results</p> <p>During the 5-year study period (2004-2008), 577 patients with dementia were included (median age: 81 years (IQR: 74-87); 69% female). Dementia was classified as unspecified dementia (57.2%), vascular dementia (25.1%), dementia in Alzheimer's disease (10.4%), and dementia in Parkinson's disease (7.3%). The prevalence of anti-dementia drugs was 25.6%. The phytopharmaceutical <it>Ginkgo biloba </it>was the most frequently prescribed anti-dementia drug overall (67.6% of all) followed by cholinesterase inhibitors (17.6%). The adjusted odds ratio (AOR) for receiving any anti-dementia drug was greater than 1 for neurologists (AOR = 2.34; CI: 1.59-3.47), the diagnosis of Alzheimer's disease (AOR = 3.28; CI: 1.96-5.50), neuroleptic therapy (AOR = 1.87; CI: 1.22-2.88), co-morbidities hypertension (AOR = 2.03; CI: 1.41-2.90), and heart failure (AOR = 4.85; CI: 3.42-6.88). The chance for a prescription of any anti-dementia drug decreased with the diagnosis of vascular dementia (AOR = 0.64; CI: 0.43-0.95) and diabetes mellitus (AOR = 0.55; CI: 0.36-0.86). The prescription of <it>Ginkgo biloba </it>was associated with sex (female: AOR = 0.41; CI: 0.19-0.89), patient age (AOR = 1.06; CI: 1.02-1.10), treatment by a neurologist (AOR = 0.09; CI: 0.03-0.23), and the diagnosis of Alzheimer's disease (AOR = 0.07; CI: 0.04-0.16).</p> <p>Conclusions</p> <p>This study provides a comprehensive analysis of everyday practice for treatment of dementia in primary care in physicians with a focus on CAM. The prescribing frequency for anti-dementia drugs is equivalent to those found in other German studies, while the administration of <it>Ginkgo biloba </it>is significantly higher.</p
Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data
Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample
Effects of general practitioner training and family support services on the care of home-dwelling dementia patients - Results of a controlled cluster-randomized study
<p>Abstract</p> <p>Background</p> <p>More than 90% of dementia patients are cared for by their general practitioners, who are decisively involved in the diagnosis, therapy and recommendation of support services. <it>Objective: </it>To test whether special training of general practitioners alters the care of dementia patients through their systematic recommendation of caregiver counseling and support groups.</p> <p>Method</p> <p>129 general practitioners enrolled 390 dementia patients and their informal caregivers in a prospective, three-arm cluster-randomized 2-year study. Arm A constituted usual care, in Arm B and C support groups and caregiver counseling (in Arm B one year after baseline, in Arm C at baseline) were recommended by the general practitioners. The general practitioners received arm-specific training. Diagnostic and therapeutic behavior of physicians was recorded at baseline. Informal caregivers were questioned in follow-up after 2 years about the utilization of support services.</p> <p>Results</p> <p>The diagnostic behavior of the general practitioners conforms to relevant guidelines. The procedure in newly-diagnosed patients does not differ from previously diagnosed patients with the exception of the rate of referral to a specialist. About one-third of the newly-diagnosed dementia patients are given an anti-dementia drug. The utilization of support groups and counseling increased five- and fourfold, respectively. Utilization of other support services remained low (< 10%), with the exception of home nursing and institutional short-term nursing.</p> <p>Conclusion</p> <p>Trained general practitioners usually act in conformity with guidelines with respect to diagnosing dementia, and partly in conformity with the guidelines with respect to recommended drug therapy. Recommendations of support services for informal caregivers by the general practitioner are successful. They result in a marked increase in the utilization rate for the recommended services compared to offers which are not recommended by the general practitioner.</p> <p>Trial registration</p> <p>ISRCTN68329593</p
- …