2,850 research outputs found
Data from an Observational Study
Introduction Effective management and development of new treatment strategies
for response fluctuations in advanced Parkinson’s disease (PD) largely depends
on clinical rating instruments such as the PD home diary. The Parkinson’s
kinetigraph (PKG) measures movement accelerations and analyzes the spectral
power of the low frequencies of the accelerometer data. New algorithms convert
each hour of continuous PKG data into one of the three motor categories used
in the PD home diary, namely motor Off state and On state with and without
dyskinesia. Objective To compare quantitative motor state assessment in
fluctuating PD patients using the PKG with motor state ratings from PD home
diaries. Methods Observational cohort study on 24 in-patients with documented
motor fluctuations who completed diaries by rating motor Off, On without
dyskinesia, On with dyskinesia, and asleep for every hour for 5 consecutive
days. Simultaneously collected PKG data (recorded between 6 am and 10 pm) were
analyzed and calibrated to the patient’s individual thresholds for Off and
dyskinetic state by novel algorithms classifying the continuous accelerometer
data into these motor states for every hour between 6 am and 10 pm. Results
From a total of 2,040 hours, 1,752 hours (87.4%) were available for analyses
from calibrated PKG data (7.5% sleeping time and 5.1% unclassified motor state
time were excluded from analyses). Distributions of total motor state hours
per day measured by PKG showed moderate-to-strong correlation to those
assessed by diaries for the different motor states (Pearson’s correlations
coefficients: 0.404–0.658), but inter-rating method agreements on the single-
hour-level were only low-to-moderate (Cohen’s κ: 0.215–0.324). Conclusion The
PKG has been shown to capture motor fluctuations in patients with advanced PD.
The limited correlation of hour-to-hour diary and PKG recordings should be
addressed in further studies
Accumulation and depletion of the toxic amino acid indospicine in calves fed creeping indigo (Indigofera spicata)
quasiharmonic equations of state for dynamically-stabilized soft-mode materials
We introduce a method for treating soft modes within the analytical framework
of the quasiharmonic equation of state. The corresponding double-well
energy-displacement relation is fitted to a functional form that is harmonic in
both the low- and high-energy limits. Using density-functional calculations and
statistical physics, we apply the quasiharmonic methodology to solid periclase.
We predict the existence of a B1--B2 phase transition at high pressures and
temperatures
Effects of safinamide on pain in patients with fluctuating Parkinson's disease
Background: Non-motor symptoms (NMS) are integral to Parkinson's Disease (PD) and management remains a challenge. Safinamide is a novel molecule in relation to addressing NMS due to its multifocal mechanism of action with both dopaminergic and non-dopaminergic properties. Objective: To investigate the efficacy of safinamide on NMS and its burden in PD patients with motor fluctuations after 6 months of treatment. Methods: This observational, multicenter, open-label, pilot study assessed a wide range of NMS using the following rating scales, NMSS (non-motor symptom scale), KPPS (King's PD pain scale), HADS (hospital anxiety and depression scale), PDQ-8 (Parkinson's disease quality of life questionnaire), and PDSS-2 (Parkinson's disease sleep scale), EuroQol-5D 3 level version (EQ-5D-3L), CGI-I (clinical global impression of improvement), and PGI-C (patient global impression of change). Motor examination using UPDRS part III (Unified Parkinson's disease rating scale, motor examination), UPDRS IV (complications of therapy) and Hoehn and Yahr staging were also obtained. Results: 27 patients were included in the analysis and were evaluated at baseline and ≥ 6 months after safinamide treatment. 26 patients had a daily maintenance dose of 100 mg and 1 patient a daily dose of 50 mg. Significant improvements in UPDRS IV, KPPS item 5 (region-specific "off" dystonia), KPPS domain 3 (items 4-6, fluctuation related pain) and KPPS total score were observed after treatment with safinamide, while maintaining stable dopaminergic medication. No statistically significant differences were found in NMSS, HADS, PDSS-2, EQ-5D-3L, and PDQ-8 after treatment. Conclusions: Our results suggest that safinamide may have a beneficial effect on pain, a key unmet need in fluctuating PD patients.The study was funded by Zambon SpA with an unconditional research grant. In addition, the study was funded by MultiPark, the strategic research area for neuroscience at Lund University; the Swedish Parkinson Foundation; the Swedish Parkinson Academy and the Faculty of Medicine at Lund University.I was not given any grant numbers or any other details. The funds were used to finance the study personell and the logistic needs of the study.S
Evidence of a high incidence of subclinically affected calves in a herd of cattle with fatal cases of Bovine Neonatal Pancytopenia (BNP).
BACKGROUND: Bovine Neonatal Pancytopenia (BNP) is a disease of calves characterised by bone marrow trilineage hypoplasia, mediated by ingestion of alloantibodies in colostrum. Suspected subclinical forms of BNP have been reported, suggesting that observed clinical cases may not represent the full extent of the disease. However to date there are no objective data available on the incidence of subclinical disease or its temporal distribution. This study aimed to 1) ascertain whether subclinical BNP occurs and, if so, to determine the incidence on an affected farm and 2) determine whether there is evidence of temporal clustering of BNP cases on this farm. To achieve these aims, haematological screening of calves born on the farm during one calving season was carried out, utilising blood samples collected at defined ages. These data were then analysed in comparison to data from both known BNP-free control animals and histopathologically confirmed BNP cases. An ordinal logistic regression model was used to create a composite haematology score to predict the probabilities of calves being normal, based on their haematology measurements at 10–14 days old. RESULTS: This study revealed that 15% (21 of 139) of the clinically normal calves on this farm had profoundly abnormal haematology (<5% chance of being normal) and could be defined as affected by subclinical BNP. Together with clinical BNP cases, this gave the study farm a BNP incidence of 18%. Calves with BNP were found to be distributed throughout the calving period, with no clustering, and no significant differences in the date of birth of cases or subclinical cases were found compared to the rest of the calves. This study did not find any evidence of increased mortality or increased time from birth to sale in subclinical BNP calves but, as the study only involved a single farm and adverse effects may be determined by other inter-current diseases it remains possible that subclinical BNP has a detrimental impact on the health and productivity of calves under certain circumstances. CONCLUSIONS: Subclinical BNP was found to occur at a high incidence in a herd of cattle with fatal cases of BNP
Disruption of Toxoplasma gondii Parasitophorous Vacuoles by the Mouse p47-Resistance GTPases
The p47 GTPases are essential for interferon-γ-induced cell-autonomous immunity against the protozoan parasite, Toxoplasma gondii, in mice, but the mechanism of resistance is poorly understood. We show that the p47 GTPases, including IIGP1, accumulate at vacuoles containing T. gondii. The accumulation is GTP-dependent and requires live parasites. Vacuolar IIGP1 accumulations undergo a maturation-like process accompanied by vesiculation of the parasitophorous vacuole membrane. This culminates in disruption of the parasitophorous vacuole and finally of the parasite itself. Over-expression of IIGP1 leads to accelerated vacuolar disruption whereas a dominant negative form of IIGP1 interferes with interferon-γ-mediated killing of intracellular parasites. Targeted deletion of the IIGP1 gene results in partial loss of the IFN-γ-mediated T. gondii growth restriction in mouse astrocytes
Primary skin fibroblasts as a model of Parkinson's disease
Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues
Thermal AdS(3), BTZ and competing winding modes condensation
We study the thermal physics of AdS(3) and the BTZ black hole when embedded
in String theory. The exact calculation of the Hagedorn temperature in TAdS(3)
is reinterpreted as the appearance of a winding tachyon both in AdS(3) and BTZ.
We construct a dual framework for analyzing the phases of the system. In this
dual framework, tachyon condensation and geometric capping appear on the same
footing, bridging the usual gap of connecting tachyon condensation to
modifications of geometry. This allows us to construct in a natural way a
candidate for the unstable phase, analogous to a small black hole in higher
dimensions. Additional peculiar effects associated with the Hagedorn
temperature and the Hawking-Page transition, some to do with the asymptotic
structure of AdS(3) and some with strong curvature effects, are analyzed and
explained.Comment: 40 pages, 5 figures, JHEP3 format. v2: added references, minor
corrections and clarification
- …