86 research outputs found
Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease.
To identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinsonâs disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable âQoL respondersâ/ânon-respondersâ. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as âQoL non-respondersâ. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as âdifficulties experiencing pleasureâ and âproblems sustaining concentrationâ. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy
Co-habiting amphibian species harbor unique skin bacterial communities in wild populations
Although all plant and animal species harbor microbial symbionts, we know surprisingly little about the specificity of microbial communities to their hosts. Few studies have compared the microbiomes of different species of animals, and fewer still have examined animals in the wild. We sampled four pond habitats in Colorado, USA, where multiple amphibian species were present. In total, 32 amphibian individuals were sampled from three different species including northern leopard frogs (Lithobates pipiens), western chorus frogs (Pseudacris triseriata) and tiger salamanders (Ambystoma tigrinum). We compared the diversity and composition of the bacterial communities on the skin of the collected individuals via barcoded pyrosequencing of the 16S rRNA gene. Dominant bacterial phyla included Acidobacteria, Actinobacteria, Bacteriodetes, Cyanobacteria, Firmicutes and Proteobacteria. In total, we found members of 18 bacterial phyla, comparable to the taxonomic diversity typically found on human skin. Levels of bacterial diversity varied strongly across species: L. pipiens had the highest diversity; A. tigrinum the lowest. Host species was a highly significant predictor of bacterial community similarity, and co-habitation within the same pond was not significant, highlighting that the skin-associated bacterial communities do not simply reflect those bacterial communities found in their surrounding environments. Innate species differences thus appear to regulate the structure of skin bacterial communities on amphibians. In light of recent discoveries that some bacteria on amphibian skin have antifungal activity, our finding suggests that host-specific bacteria may have a role in the species-specific resistance to fungal pathogens
Homeostatic regulation of the endoneurial microenvironment during development, aging and in response to trauma, disease and toxic insult
The endoneurial microenvironment, delimited by the endothelium of endoneurial vessels and a multi-layered ensheathing perineurium, is a specialized milieu intĂ©rieur within which axons, associated Schwann cells and other resident cells of peripheral nerves function. The endothelium and perineurium restricts as well as regulates exchange of material between the endoneurial microenvironment and the surrounding extracellular space and thus is more appropriately described as a bloodânerve interface (BNI) rather than a bloodânerve barrier (BNB). Input to and output from the endoneurial microenvironment occurs via bloodânerve exchange and convective endoneurial fluid flow driven by a proximo-distal hydrostatic pressure gradient. The independent regulation of the endothelial and perineurial components of the BNI during development, aging and in response to trauma is consistent with homeostatic regulation of the endoneurial microenvironment. Pathophysiological alterations of the endoneurium in experimental allergic neuritis (EAN), and diabetic and lead neuropathy are considered to be perturbations of endoneurial homeostasis. The interactions of Schwann cells, axons, macrophages, and mast cells via cellâcell and cellâmatrix signaling regulate the permeability of this interface. A greater knowledge of the dynamic nature of tight junctions and the factors that induce and/or modulate these key elements of the BNI will increase our understanding of peripheral nerve disorders as well as stimulate the development of therapeutic strategies to treat these disorders
Present state and future perspectives of using pluripotent stem cells in toxicology research
The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitroâcultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed
Observation of B(s)0âJ/ÏppÂŻ decays and precision measurements of the B(s)0 masses
The first observation of the decays
B
0
(
s
)
â
J
/
Ï
p
ÂŻ
p
is reported, using proton-proton collision data corresponding to an integrated luminosity of
5.2
â
â
fb
â
1
, collected with the LHCb detector. These decays are suppressed due to limited available phase space, as well as due to Okubo-Zweig-Iizuka or Cabibbo suppression. The measured branching fractions are
B
(
B
0
â
J
/
Ï
p
ÂŻ
p
)
=
[
4.51
±
0.40
(
stat
)
±
0.44
(
syst
)
]
Ă
10
â
7
,
B
(
B
0
s
â
J
/
Ï
p
ÂŻ
p
)
=
[
3.58
±
0.19
(
stat
)
±
0.39
(
syst
)
]
Ă
10
â
6
. For the
B
0
s
meson, the result is much higher than the expected value of
O
(
10
â
9
)
. The small available phase space in these decays also allows for the most precise single measurement of both the
B
0
mass as
5279.74
±
0.30
(
stat
)
±
0.10
(
syst
)
â
â
MeV
and the
B
0
s
mass as
5366.85
±
0.19
(
stat
)
±
0.13
(
syst
)
â
â
MeV
Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease
AbstractTo identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinsonâs disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable âQoL respondersâ/ânon-respondersâ. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as âQoL non-respondersâ. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as âdifficulties experiencing pleasureâ and âproblems sustaining concentrationâ. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy.</jats:p
Quantitative profiling of oxylipins through comprehensive LC-MS/MS analysis: application in cardiac surgery
Amplitude analysis of the B0 (s)! K0K0 decays and measurement of the branching fraction of the B0! K0K0 decay
The and decays are studied using proton-proton collision data
corresponding to an integrated luminosity of 3fb. An untagged and
time-integrated amplitude analysis of
decays in two-body invariant mass regions of 150 MeV around the
mass is performed. A stronger longitudinal polarisation fraction in the decay, , is observed as compared to in the decay. The ratio of branching fractions of the two decays
is measured and used to determine .Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2019-004.html (LHCb
public pages
Search for Lepton-Universality Violation in B^{+}âK^{+}â^{+}â^{-} Decays.
A measurement of the ratio of branching fractions of the decays B^{+}âK^{+}ÎŒ^{+}ÎŒ^{-} and B^{+}âK^{+}e^{+}e^{-} is presented. The proton-proton collision data used correspond to an integrated luminosity of 5.0ââfb^{-1} recorded with the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. For the dilepton mass-squared range 1.1<q^{2}<6.0ââGeV^{2}/c^{4} the ratio of branching fractions is measured to be R_{K}=0.846_{-0.054}^{+0.060}_{-0.014}^{+0.016}, where the first uncertainty is statistical and the second systematic. This is the most precise measurement of R_{K} to date and is compatible with the standard model at the level of 2.5 standard deviations
Amplitude analysis of B-s(0) -> K-S(0) K-+/-pi(-/+) decays
The first untagged decay-time-integrated amplitude analysis of decays is performed using a
sample corresponding to fb of collision data recorded with
the LHCb detector during 2011 and 2012. The data are described with an
amplitude model that contains contributions from the intermediate resonances
, and , and their
charge conjugates. Measurements of the branching fractions of the decay modes
and are in agreement with, and
more precise than, previous results. The decays and are observed for the first time, each with
significance over 10 standard deviations.Comment: 27 pages, 14 figures. All figures and tables, along with any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2018-045.htm
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