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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-mañé Laia Just-Borràs marta Balanyà-Segura Aleksandra Polishchuk laura Nadal marta Tomàs Carolina Silvera-Simón manel m.Santafé maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

Conversion of CO_(2)to added value products via rWGS using Fe-promoted catalysts:Carbide,metallic Fe or a mixture?

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Journal of Energy Chemistry 2022年第3期31卷 635-646,I0017页

作者： q iZhang laura Pastor-Pérez qiang Wang Tomas Ramirez Reina Department of Chemical and Process Engineering University of SurreyGuildford GU27XHUnited Kingdom College of Environmental Science and Engineering Beijing Forestry UniversityBeijing 100083China

Fe-based catalysts are efficient systems for CO_(2)conversion via reverse water-gas shift(rWGS)***,the nature of the active phase,namely metallic iron,iron oxide or iron carbide remains a subject of debate which our paper is meant to ***0 is a much better catalyst for the rWGS than Fe_(3)*** activity of Fe0 can be promoted by the addition of Cs and Cu whose presence hinders iron carburisation while favouring both higher conversion and enhanced *** the samples are aged in the rWGS reaction mixture during stability test a new phase appear:Fe_(5)C_(2),resulting in a more active but less selective catalysts than Fe0 for the rWGS *** our results indicate that we could potentially achieve an optimal activity/selective balance upon finely tuning the proportion Fe/Fe_(5)C_(2).Beyond the fundamental information concerning active phase we have observed the presence of advanced Fischer-Tropsch-like products at ambient pressure opening new opportunities for the design of hybrid rWGS/Fischer-Tropsch systems.

关键词： CO_(2)conversion rWGS Fe carbide Fe catalysts Hybrid catalysts

Impact of bolus volume on small intestinal intra-luminal impedance in healthy subjects

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World Journal of Gastroenterology 2010年第17期16卷 2151-2157页

作者： Nam q Nguyen laura K Bryant Carly m Burgstad Robert J Fraser Daniel Sifrim Richard H Holloway Department of Gastroenterology & Hepatology Royal Adelaide HospitalAdelaide 5000Australia Investigation and Procedures Unit Repatriation General HospitalDaw Park 5041Australia Department of medicine Centre for Gastroen-terological ResearchK.U.LeuvenLeuven 3000Belgium

AIm: To assess the impact of bolus volume on the characteristics of small intestinal (SI) impedance ***: Concurrent SI manometry-impedance measurements were performed on 12 healthy volunteers to assess the pattern of proximal jejunal fluid bolus movement over a 14 *** subject was given 34 boluses of normal saline (volume from 1 to 30 mL) via the feeding tube placed immediately above the proximal margin of the studied segment.A bolus-induced impedance event occurred if there was > 12% impedance drop from baseline,over ≥ 3 consecutive segments within 10 s of bolus injection.A minor or major imped-ance event was defined as a duration of impedance drop minimum volume required for a detectable SI impedance event was 2 mL.A direct linear relationship between the SI bolus volume and the occurrence of impedance events was noted until SI bolus volume reached 10 mL,a volume which always produced an impedance flow *** was a moderate correlation between the bolus volume and the duration of impedance drop (r = 0.63,P mber of propagated channels (r = 0.50,P me boluses were associated with more major impedance events (≥ 10 mL boluses = 63%,3 mL boluses = 17%,and mL boluses = 0%,P = 0.02).CONCLUSION: Bolus volume had an impact on the type and length of propagation of SI impedance events and a threshold of 2 mL is required to produce an event.

关键词： Bolus volume Health Impedance Luminal flow Small intestine

Proximal gastric motility in critically ill patients with type 2 diabetes mellitus

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World Journal of Gastroenterology 2007年第2期13卷 270-275页

作者： Nam q Nguyen Robert J Fraser laura K Bryant marianne Chapman Richard H Holloway Department of Gastroenterology Hepatology and General Medicine Royal Adelaide Hospital South Australia Investigation and Procedures Unit Repatriation General Hospital South Australia Anaesthesia and Intensive Care Royal Adelaide Hospital South Australia

AIm： To investigate the proximal gastric motor response to duodenal nutrients in critically ill patients with longstanding type 2 diabetes ***： Proximal gastric motility was assessed （using a barostat） in 10 critically ill patients with type 2 diabetes mellitus （59±3 years） during two 60-min duodenal infusions of Ensure （1 and 2 kcal/min）, in random order, separated by 2h fasting. Data were compared with 15 non-diabetic critically ill patients （48 ± 5 years） and 10 healthy volunteers （28 ±3 years）. RESULTS： Baseline proximal gastric volumes were similar between the three groups. In diabetic patients, proximal gastric relaxation during I kcal/min nutrient infusion was similar to non-diabetic patients and healthy controls. In contrast, relaxation during 2 kcal/ min infusion was initially reduced in diabetic patients （P 〈 0.05） but increased to a level similar to healthy humans, unlike non-diabetic patients where relaxation was impaired throughout the infusion. Duodenal nutrient stimulation reduced the fundic wave frequency in a dose-dependent fashion in both the critically ill diabetic patients and healthy subjects, but not in critically ill patients without diabetes. Fundic wave frequency in diabetic patients and healthy subjects was greater than in non-diabetic ***： In patients with diabetes mellitus, proximal gastric motility is less disturbed than nondiabetic patients during critical illness, suggesting that these patients may not be at greater risk of delayed gastric emptying.

关键词： Proximal gastric function Diabetes mellitus type 2 Critical illness Enteral nutrition

Tree: Reducing the use of restrictive practices on psychiatric wards through virtual reality immersive technology training

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World Journal of Psychiatry 2024年第10期14卷 1521-1537页

作者： Peter Phiri laura Pemberton Yang Liu Xiaojie Yang Joe Salmon Isabel Boulter Sana Sajid Jackie Clarke Andy mcmillan Jian qing Shi Gayathri Delanerolle Department of Research&Innovation Southern Health National Health Service Foundation TrustSouthampton SO303JBUnited Kingdom Department of Statistics and Data Science Southern University of Science and TechnologyShenzhen 518055Guangdong ProvinceChina School of Statistics and mathematics Yunnan University of Finance and EconomicsKunming 650221Yunnan ProvinceChina Virti Healthcare KeynshamBristol BS311SNUnited Kingdom Neuromodulation Centre Southern Health National Health Service Foundation TrustSouthampton SO140YGUnited Kingdom National Health Service Talking Therapies Southern Health National Health Service Foundation TrustSouthampton SO509FHUnited Kingdom

BACKGROUND Restrictive practices(RPs)are defined by measures linked to physical and chemical restraints to reduce the movement or control behaviours during any *** is an equal part of RPs intended to isolate and reduce the sensory stimulation to safeguard the patient and those within the *** interventions by way of virtual reality(VR)could assist with reducing the need for RPs as it could help reduce anxiety or agitation by way of placing users into realistic and immersive *** could also aid staff to and change current *** To assess the feasibility and effectiveness of using a VR platform to provide reduction in RP *** A randomised controlled feasibility study,accompanied by evaluations at 1 month and 6 months,was conducted within inpatient psychiatric wards at Southern Health National Health Service Foundation Trust,United *** VR scenarios were used on VR headsets to provide training on reducing RPs in 3 inpatient psychiatric *** measures included general self-efficacy scale,generalised anxiety disorder assessment 7(GAD-7),Burnout Assessment Tool 12,the Everyday Discrimination Scale,and the Compassionate Engagement and Action *** Findings revealed statistically significant differences between the VR and treatment as usual groups,in the Everyday Discrimination Scale items q8 and q9:P=0.023 and P=0.040 respectively,indicating higher levels of perceived discrimination in the VR *** were no significant differences between groups in terms of general self-efficacy,generalised anxiety disorder assessment 9,and Burnout Assessment Tool 12 scores.A significant difference was observed within the VR group for compassionate engagement from others(P=0.005)over *** respondents recorded System Usability Scale scores above 70,with an average score of *** was a significant reduction in rates of RPs in the VR group vs treatment as usual group with a fluctuating variability ob

关键词： Virtual reality Restrictive practices Inpatient wards Restraint Isolation Rapid tranquilisation Covert medication Procedural restrictions Health professions training

mechanisms underlying feed intolerance in the critically ill: Implications for treatment

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World Journal of Gastroenterology 2007年第29期13卷 3909-3917页

作者： Adam Deane marianne J Chapman Robert J Fraser laura K Bryant Carly Burgstad Nam q Nguyen Intensive Care Unit Royal Adelaide Hospital Adelaide South Australia Discipline of medicine University of Adelaide and Investigation and Procedures Unit Repatriation General Hospital Adelaide South Australia Investigation and Procedures Unit Repatriation General Hospital Adelaide South Australia Department of Gastroenterology and Hepatology Royal Adelaide Hospital Adelaide South Australia

malnutrition is associated with poor outcomes in critically ill patients. Although nutritional support is yet to be proven to improve mortality in non-malnourished critically ill patients, early enteral feeding is considered best practice. However, enteral feeding is often limited by delayed gastric emptying. The best method to clinically identify delayed gastric emptying and feed intolerance is unclear. Gastric residual volume （GRV） measured at the bedside is widely used as a surrogate marker for gastric emptying, but the value of GRV measurement has recently been disputed. While the mechanisms underlying delayed gastric emptying require further investigation, recent research has given a better appreciation of the pathophysiology. A number of pharmacological strategies are available to improve the success of feeding. Recent data suggest a combination of intravenous metoclopramide and en/thromycin to be the most successful treatment, but novel drug therapies should be explored. Simpler methods to access the duodenum and more distal small bowel for feed delivery are also under investigation. This review summarises current understanding of the factors responsible for, and mechanisms underlying feed intolerance in critical illness, together with the evidence for current practices. Areas requiring further research are also highlighted.

关键词： Critical illness Enteral nutrition Gastric emptying Gastric motility Gastrointestinal hormones metoclopramide Erythromycin Prokinetic therapy

Proximal gastric response to small intestinal nutrients is abnormal in mechanically ventilated critically ill patients

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World Journal of Gastroenterology 2006年第27期12卷 4383-4388页

作者： Nam q Nguyen Robert J Fraser marianne Chapman laura K Bryant Richard H Holloway Rosalie Vozzo Christine Feinle-Bisset Department of Gastroenterology Hepatology and General MedicineRoyal Adelaide HospitalSouth Australia University Department of medicine University of AdelaideSouth Australia Department of Intensive Care Royal Adelaide HospitalSouth Australia Department of Gastroenterology Hepatology and General MedicineRoyal Adelaide HospitalSouth Australia Department of GastroenterologyUniversity of AdelaideSouth Australia

AIm： To determine the response of the proxima stomach to small intestinal nutrients in critically ill patients. mETHODS： Proximal gastric motility was measured in 13 critically ill patients （49.3 ± 4.7 years） and 12 healthy volunteers （27.7 ± 2.9 years） using a barostat technique. Recordings were performed at baseline, during a 60-rain intra-duodenal infusion of Ensure^R （2 kcal/min）, and for 2 h following the infusion. minimum distending pressure （mDP）, intra-bag volume and fundic wave activity were determined. RESULTS： The mDP was higher in patients （11.7 ± 1.1 vs 7.8 ± 0.7 mmHg; P 〈 0.01）. Baseline intrabag volumes were similar in the 2 groups. In healthy subjects, a ‘bimodal＇ proximal gastric volume response was observed. In patients, the initial increase in proximal gastric volume was small and delayed, but eventually reached a maximal volume similar to that of healthy subjects. In healthy subjects, the proximal gastric volume rapidly returned to baseline level after nutrient infusion （median 18 min）. In contrast, the recovery of volume to baseline was delayed in critically ill patients （median 106 min）. In 6 patients, the volume had not returned to baseline level 2 hours after nutrient infusion. In patients, fundic volume waves were less frequent （P 〈 0.05） and had lower amplitude （P 〈 0.001）, compared to healthy subjects. CONCLUSION： In critical illness, proximal gastric motor responses to small intestinal nutrient stimulation are abnormal.

关键词： Proximal gastric response Small intestinal nutrient Critical illness

Daily genetic profiling indicates JAK/STAT signaling promotes early hepatic stellate cell transdifferentiation

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World Journal of Gastroenterology 2010年第40期16卷 5047-5056页

作者： Ashley m Lakner Cathy C moore Alyssa A Gulledge laura W Schrum Department of Biology University of North Carolina at Charlotte Digestive and metabolic Disorders Laboratory Carolinas Medical Center

AIm: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation. mETHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AmADA software. The significance of JAK/STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor. RESULTS: Genetic cluster analyses, based on expression of these 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day q) and day 4 cells were genotypically distinct from any of the other days. Additionally, gene expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRNA in the early stages of activation. Inhibition of the JAK/STAT signaling pathway impeded the morphological transdifferentiation of HSCs which correlated with decreased mRNA expression of several profibrotic genes including collagens, α-SmA, PDGFR and TGFβR. CONCLUSION: These data demonstrate unique clustered genetic profiles during the daily progression of HSC transdifferentiation and that JAK/STAT signaling may be critical in the early stages of transdifferentiation.

关键词： Cluster analysis Fibrosis Genetic profile Hepatic stellate cell Interleukin-6

Hierarchical state-abstracted and socially augmented q-Learning for reducing complexity in agent-based learning

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控制理论与应用（英文版） 2011年第3期9卷 440-450页

作者： laura RAY Thayer School of Engineering Dartmouth College

A primary challenge of agent-based policy learning in complex and uncertain environments is escalating computational complexity with the size of the task space(action choices and world states) and the number of ***,there is ample evidence in the natural world that high-functioning social mammals learn to solve complex problems with ease,both individually and *** ability to solve computationally intractable problems stems from both brain circuits for hierarchical representation of state and action spaces and learned policies as well as constraints imposed by social *** biologically derived mechanisms for state representation and mammalian social intelligence,we constrain state-action choices in reinforcement learning in order to improve learning *** results bound the reduction in computational complexity due to stateion,hierarchical representation,and socially constrained action selection in agent-based learning problems that can be described as variants of markov decision *** of two task domains,single-robot herding and multirobot foraging,shows that theoretical bounds hold and that acceptable policies emerge,which reduce task completion time,computational cost,and/or memory resources compared to learning without hierarchical representations and with no social knowledge.

关键词： Decentralized markov decision process Reinforcement learning multiagent systems