Purpose
Deep sedation for endoscopic retrograde cholangiopancreatography (ERCP) can be challenging in elderly patients in the prone position. This study investigated the effect of a high flow nasal ...oxygen (HFNO) delivery system on oxygenation in this procedure compared with that of conventional nasal cannula oxygen administration.
Methods
A prospective randomized trial was conducted using HFNO and conventional nasal cannula in patients undergoing ERCP in the prone position. For each patient, the lowest oxygen saturation (SpO
2
), the incidence of hypoxemia defined as an SpO
2
below 90%, and interruptions due to airway interventions were recorded during the procedure.
Results
The lowest mean (standard deviation) SpO
2
recorded during the procedure was higher in the HFNO group than in the conventional control group 99.8 (0.6)%
vs
95.1 (7.3)%; mean difference, 4.7%; 95% confidence interval, 2.3% to 7.1%;
P
Group x Time
< 0.001. While the lowest SpO
2
during the procedure was lower than the baseline SpO
2
in the control group, the lowest SpO
2
during the procedure was higher than the baseline SpO
2
in the HFNO group. Hypoxemia occurred only in the control group (
n
= 7; 19%;
P
= 0.01). Procedural interruptions, including discontinuation of sedation, patient stimulation, and jaw thrusting, occurred only in the control group (
n
= 9 25%,
n
= 10 28%, and
n
= 10 28% cases, respectively;
P
= 0.001 for each).
Conclusion
In contrast to conventional nasal cannula, high flow nasal oxygen provided adequate oxygenation without causing procedural interruptions during ERCP, suggesting that HFNO may be used as a standard oxygen delivery method during these procedures.
Trial registration
www.ClinicalTrials.gov
(NCT03872674); registered 11 March 2019.
In Noonan syndrome (NS) 30-50% of subjects show cognitive deficits of unknown etiology and with no known treatment. Here, we report that knock-in mice expressing either of two NS-associated mutations ...in Ptpn11, which encodes the nonreceptor protein tyrosine phosphatase Shp2, show hippocampal-dependent impairments in spatial learning and deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of an NS-associated allele PTPN11(D61G) in adult mouse hippocampus results in increased baseline excitatory synaptic function and deficits in LTP and spatial learning, which can be reversed by a mitogen-activated protein kinase kinase (MEK) inhibitor. Furthermore, brief treatment with lovastatin reduces activation of the GTPase Ras-extracellular signal-related kinase (Erk) pathway in the brain and normalizes deficits in LTP and learning in adult Ptpn11(D61G/+) mice. Our results demonstrate that increased basal Erk activity and corresponding baseline increases in excitatory synaptic function are responsible for the LTP impairments and, consequently, the learning deficits in mouse models of NS. These data also suggest that lovastatin or MEK inhibitors may be useful for treating the cognitive deficits in NS.
Abstract
Postsynaptic density protein 95 (PSD-95) is a pivotal postsynaptic scaffolding protein in excitatory neurons. Although the transport and regulation of PSD-95 in synaptic regions is well ...understood, dendritic transport of PSD-95 before synaptic localization still remains to be clarified. To evaluate the role of KIF5, conventional kinesin, in the dendritic transport of PSD-95 protein, we expressed a transport defective form of KIF5A (ΔMD) that does not contain the N-terminal motor domain. Expression of ΔMD significantly decreased PSD-95 level in the dendrites. Consistently, KIF5 was associated with PSD-95 in in vitro and in vivo assays. This interaction was mediated by the C-terminal tail regions of KIF5A and the third PDZ domain of PSD-95. Additionally, the ADPDZ3 (the association domain of NMDA receptor and PDZ3 domain) expression significantly reduced the levels of PSD-95, glutamate receptor 1 (GluA1) in dendrites. The association between PSD-95 and KIF5A was dose-dependent on Staufen protein, suggesting that the Staufen plays a role as a regulatory role in the association. Taken together, our data suggest a new mechanism for dendritic transport of the AMPA receptor-PSD-95.
Recently, the fourth industrial revolution has accelerated the application of multiple degrees-of-freedom (DOF) robot arms in various applications. However, it is difficult to utilize robot arms for ...precision motion control because of their low stiffness. External loads applied to robot arms induce deflections in the joints and links, which deteriorates the positioning accuracy. To solve this problem, control methods using a disturbance observer (DOB) with an external sensory system have been developed. However, external sensors are expensive and have low reliability because of noise and reliance on the surrounding environment. A disturbance-observer-based dual-position feedback (DOB-DPF) controller is proposed herein to improve the positioning accuracy by compensating for the deflections in real time using only an internal sensor. The DOB was designed to derive the unpredictable disturbance torque applied to each joint using the command voltage generated by the position controller. The angular deflection of each joint was calculated based on the disturbance torque and joint stiffness, which were identified experimentally. The DPF controller was designed to control the joint motor while simultaneously compensating for angular deflection. A five-DOF robot arm testbed with a position controller was constructed to verify the proposed controller. The contouring performance of the DOB-DPF controller was compared with that of a conventional position controller with an external load applied to the end effector. The increases in the root mean square values of the contour errors were 1.71 and 0.12 mm with a conventional position controller and the proposed DOB-DPF controller, respectively, after a 2.2 kg weight was applied to the end effector. The results show that the contour error caused by the external load is effectively compensated for by the DOB-DPF controller without an external sensor.
Dear Editor,
Eliminating misfolded or mistargeted proteins is crucial for cell viability because these proteins accumulate as non-specific aggregates, which can be toxic to the cell （Lee et al., ...2009; Sroka et al., 2009）. Previously, we have shown that in ppi2 （plastid protein import 2） mutant plants, the transcript levels of Hsc70-4 （one isoform of the Hsc70 family） and CHIP （an E3 ligase） were highly upregulated, which ultimately plays crucial roles in proteasomal degradation of unimported plastid proteins （Lee et al., 2009）. We also found that, along with those of Hsc70-4 and CHIP, the transcript level of AtBAG1 （Arabidopsis thaliana Bcl2-associated athanogene 1） in the ppi2 mutant was 2.38-fold higher than that in the wild-type （Lee et al., 2009）.
This study aims to present a strategy to transform the worldviews of students, especially college science classrooms, into desirable current worldviews (Darwin, Quantum mechanics, Einstein, refer to ...Fig 1). Above all, the worldviews, that is metaphysical belief, needs to be changed. This is because metaphysical belief is the basis for the whole framework of conception. Since the previous study emphasized epistemological belief only, an emphasis was placed on metaphysical belief on which epistemological belief is based. Therefore, the two beliefs should be used to elucidate in the education of Nature of Science. Metaphysical belief in the science of cosmic order, symmetry, or disorder is often important in scientific research and can lead to an epistemological view that can select or reject a certain kind of explanation. Specially, the two-slit experiment with single electrons is a radical illustration of another paradigm shift, from classical (mechanistic materialism) to quantum physics (desirable dialectical materialism). The double slit electron experiment creates sensuous images that can be grasped at once. Because quantum mechanics is inherently abstract, it is difficult to accept its meaning.
There is increasing evidence that upregulation of arginase contributes to impaired endothelial function in aging. In this study, we demonstrate that arginase upregulation leads to endothelial nitric ...oxide synthase (eNOS) uncoupling and that in vivo chronic inhibition of arginase restores nitroso-redox balance, improves endothelial function, and increases vascular compliance in old rats. Arginase activity in old rats was significantly increased compared with that shown in young rats. Old rats had significantly lower nitric oxide (NO) and higher superoxide (O2(-)) production than young. Acute inhibition of both NOS, with N(G)-nitro-l-arginine methyl ester, and arginase, with 2S-amino- 6-boronohexanoic acid (ABH), significantly reduced O2(-) production in old rats but not in young. In addition, the ratio of eNOS dimer to monomer in old rats was significantly decreased compared with that shown in young rats. These results suggest that eNOS was uncoupled in old rats. Although the expression of arginase 1 and eNOS was similar in young and old rats, inducible NOS (iNOS) was significantly upregulated. Furthermore, S-nitrosylation of arginase 1 was significantly elevated in old rats. These findings support our previously published finding that iNOS nitrosylates and activates arginase 1 (Santhanam et al., Circ Res 101: 692-702, 2007). Chronic arginase inhibition in old rats preserved eNOS dimer-to-monomer ratio and significantly reduced O2(-) production and enhanced endothelial-dependent vasorelaxation to ACh. In addition, ABH significantly reduced vascular stiffness in old rats. These data indicate that iNOS-dependent S-nitrosylation of arginase 1 and the increase in arginase activity lead to eNOS uncoupling, contributing to the nitroso-redox imbalance, endothelial dysfunction, and vascular stiffness observed in vascular aging. We suggest that arginase is a viable target for therapy in age-dependent vascular stiffness.
Guanine nucleotide exchange factors (GEFs) play important roles in many cellular processes, including regulation of the structural plasticity of dendritic spines. A GEF protein, adenomatous polyposis ...coli‐stimulated GEF 1 (Asef1, ARHGEF4) is highly expressed in the nervous system. However, the function of Asef1 has not been investigated in neurons. Here, we present evidence showing that Asef1 negatively regulates the synaptic localization of postsynaptic density protein 95 (PSD‐95) in the excitatory synapse by inhibiting Staufen‐mediated synaptic localization of PSD‐95. Accordingly, Asef1 expression impairs synaptic transmission in hippocampal cultured neurons. In addition, neuronal activity facilitates the dissociation of Asef1 from Staufen in a phosphoinositide 3 kinase (PI3K)‐dependent manner. Taken together, our data reveal Asef1 functions as a negative regulator of synaptic localization of PSD‐95 and synaptic transmission.
Guanine nucleotide exchange factors (GEFs) play important roles in the regulation of the structural plasticity of dendritic spines. We provided a role of the GEF protein adenomatous polyposis coli‐stimulated guanine nucleotide exchange factor 1 (Asef1) as a negative regulator in excitatory synapses: Asef1 inhibits PSD‐95 localization by binding with Staufen. Additionally, neuronal activity modulates the association of Asef1 with Staufen in a phosphoinositide 3 kinase (PI3K)‐dependent manner. Taken together, our data reveal Asef1 functions as a negative regulator of synaptic localization of PSD‐95 and synaptic transmission.
Background: The aims of this research are 1) to explore the inter-relationships within the individual elements or tenets of Nature of Science (NOS), based on the dimensions of scientific knowledge in ...science learning, and 2) to consider Kuhn's concept of how scientific revolution takes place. Material and methods: This study suggests that instruction according to our NOS Flowchart should include the tenets of NOS. The aspects of NOS that have been emphasized in recent science education reform documents disagree with the received views of common science. Attitudes about science can have a significant effect on scientific literacy. In education theory, the understanding of content lies in the cognitive domain, whereas attitudes lie in the affective domain. Results: There are three major dimensions of learning in science: knowledge, skills, and attitudes. Additionally, it is valuable to introduce students at the primary level to some of the ideas developed by Kuhn. Key aspects of NOS are, in fact, good applications to the history of science through Kuhn’s philosophy. Conclusions: Therefore, an NOS Flow Map could be a promising means of understanding the NOS tenets and an explicit and reflective tool for science teachers to enhance scientific teaching and learning.
PDF
