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1.
PLoS One ; 16(9): e0257887, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34582505

RESUMO

STUDY OBJECTIVE: The purpose of this feasibility study is to develop and validate a new assessment tool and scoring system for multitasking competency for physicians in-training in a timed simulated setting. The multitasking competency includes ability to appropriately prioritize and implement tasks for different patients who present simultaneously. METHODS: We designed three single task stations with different levels of difficulty and priority. These skill stations were then combined to create a multitasking simulation scenario. Skill checklists and the global rating scale were utilized to assess the participants' performance. A multitasking score, multitasking index, and priority score were developed to measure the multitasking ability of participants. RESULTS: Thirty-three first-year postgraduate physicians were recruited for this prospective study. The total performance scores were significantly higher for the single-tasking stations than for the multitasking scenario. In terms of the time needed to complete the tasks, the participants spent more time on the multitasking scenario than on the single-tasking scenario. There were significant correlations between the global rating scale and the multitasking score (rho = 0.693, p < 0.001) and between the global rating scale and the multitasking index (rho = 0.515, p < 0.001). The multitasking score, multitasking index, and priority score did not have any significant correlations with the total single-tasking score. CONCLUSION: We demonstrated that the use of a simulated multitasking scenario could be an effective method of assessing multitasking ability and allow assessors to offer better quality feedback.


Assuntos
Competência Clínica , Medicina de Emergência/educação , Adulto , Simulação por Computador , Estudos de Viabilidade , Feminino , Humanos , Masculino , Comportamento Multitarefa , Estudos Prospectivos
2.
Pharmaceutics ; 13(8)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34452143

RESUMO

The blood-brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among some of the limitations associated with current neurotherapeutics. In recent years, advances in nanodrug delivery have enabled the carrier system containing the active therapeutic drug to target the signaling pathways and pathophysiology that are closely linked to central nervous system (CNS) disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), brain tumor, epilepsy, ischemic stroke, and neurodegeneration. At present, among the nano formulations, solid lipid nanoparticles (SLNs) have emerged as a putative drug carrier system that can deliver the active therapeutics (drug-loaded SLNs) across the BBB at the target site of the brain, offering a novel approach with controlled drug delivery, longer circulation time, target specificity, and higher efficacy, and more importantly, reducing toxicity in a biomimetic way. This paper highlights the synthesis and application of SLNs as a novel nontoxic formulation strategy to carry CNS drugs across the BBB to improve the use of therapeutics agents in treating major neurological disorders in future clinics.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34205325

RESUMO

Patients might be willing to pay more to obtain better quality medical services when they recognize that high-level hospitals have better quality. However, published papers have not found solid empirical evidence to support this possibility. Therefore, the purpose of this study is to empirically investigate patients' willingness to pay (WTP) for an outpatient copayment. The study aims to analyze the difference between the two WTP values: to implement a hierarchy of medical care and to improve the quality of medical services. This study administered a questionnaire using the contingent valuation method with a quasi-bidding game for patients' WTP and the SERVQUAL scale for medical service quality. The Wilcoxon signed-rank test was employed to test the difference between the two WTP values, notably to implement a hierarchy of medical care and to improve the quality of medical services. Both of the WTP values are higher than the academic medical centre's current copayment NT$420 (approximately US$14); the percentage of respondents willing to pay a higher copayment declined when the outpatient copayment was increased, and the patients' WTP to have better medical service quality was significantly higher than that to implement a hierarchy of medical care. Patients' desire to receive better medical services from higher-level hospitals might be stronger than their desire to implement hierarchical medical care. This study reported the relationship between the respondents' perceived medical service quality and WTP for having better service quality by using regression models. The respondents' perceptions of medical service quality, especially for "reliability" and "assurance," would positively affect their WTP. Policy makers should focus on improving the quality of medical services.


Assuntos
Financiamento Pessoal , Pacientes Ambulatoriais , Serviços de Saúde , Humanos , Inquéritos e Questionários , Taiwan
4.
ACS Chem Neurosci ; 12(14): 2643-2660, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34197084

RESUMO

Therapeutic options for Parkinson's disease (PD) are limited to a symptomatic approach, making it a global threat. Targeting aggregated alpha-synuclein (α-syn) clearance is a gold standard for ameliorating PD pathology, bringing autophagy into the limelight. Expression of autophagy related genes are under the regulation by histone modifications, however, its relevance in PD is yet to be established. Here, preformed fibrillar form (PFF) of α-syn was used to induce PD in wistar rats, which were thereafter subjected to treatment with trehalose (tre, 4g/kg, orally), a potent autophagy inducer and sodium butyrate (SB, 300 mg/kg, orally), a pan histone deacetylase inhibitor alone as well as in combination. The combination treatment significantly reduced motor deficits as evidenced after rotarod, narrow beam walk, and open field tests. Novel object location and recognition tests were performed to govern cognitive abnormality associated with advanced stage PD, which was overcome by the combination treatment. Additionally, with the combination, the level of pro-inflammatory cytokines were significantly reduced, along with elevated levels of dopamine and histone H3 acetylation. Further, mRNA analysis revealed that levels of certain autophagy related genes and proteins implicated in PD pathogenesis significantly improved after administration of both tre and SB. Immunofluorescence and H&E staining in the substantia nigra region mirrored a potential improvement after treatment with both tre and SB. Therefore, outcomes of the present study were adequate to prove that combinatorial efficacy with tre and SB may prove to be a formidable insight into ameliorating PD exacerbated by PFF α-syn as compared to its individual efficacy.


Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Animais , Ácido Butírico/farmacologia , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Ratos , Ratos Wistar , Trealose/farmacologia , alfa-Sinucleína
5.
J Cell Mol Med ; 25(15): 7418-7425, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34216182

RESUMO

We previously showed a hydroxamic acid-based histone deacetylase inhibitor (HDACi), compound 13, provides neuroprotection against chronic cerebral hypoperfusion (CCH) both in vitro under oxygen-glucose deprivation (OGD) conditions and in vivo under bilateral common carotid artery occlusion (BCCAO) conditions. Intriguingly, the protective effect of this HDACi is via H3K14 or H4K5 acetylation-mediated differential BDNF isoform activation. BDNF is involved in cell proliferation and differentiation in development, synaptic plasticity and in learning and memory related with receptors or synaptic proteins. B6 mice underwent BCCAO and were randomized into 4 groups; a sham without BCCAO (sham), BCCAO mice injected with DMSO (DMSO), mice injected with HDACi-compound 13 (compound 13) and mice injected with suberoylanilide hydroxamic acid (SAHA). The cortex and hippocampus of mice were harvested at 3 months after BCCAO, and levels of BDNF, AMPA receptor and dopamine receptors (D1, D2 and D3) were studied using Western blotting analysis or immunohistochemistry. We found that the AMPA receptor plays a key role in the molecular mechanism of this process by modulating HDAC. This protective effect of HDACi may be through BDNF; therefore, activation of this downstream signalling molecule, for example by AMPA receptors, could be a therapeutic target or intervention applied under CCH conditions.

6.
Medicine (Baltimore) ; 100(20): e25898, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011056

RESUMO

BACKGROUND: Although tranexamic acid (TXA), a readily accessible antifibrinolytic agent, is widely adopted in hemorrhage scenarios, its role on mortality in patients with hemoptysis remains uncertain. New evidence is yet to be generated to evaluate the risk of mortality after using TXA in patients with hemoptysis. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were searched from inception to May 2020. Randomized controlled trials and observational studies that evaluated the effect of TXA on patients with hemoptysis were included. Data were independently extracted by 2 reviewers and synthesized using a random-effects model. MAIN RESULTS: Five studies with a total of 20,047 patients were analyzed. When compared with the control, administration of TXA was associated with a reduction in short-term mortality (risk ratio = 0.78, 95% confidence interval [CI] 0.72-0.85; I2 = 0), shorter bleeding time (mean difference = - 24.61 hours, 95% CI - 35.96 to -13.26, I2 = 0), shorter length of hospital stay (mean difference = -1.94 days, 95% CI -2.48 to -1.40, I2 = 0), and lower need for intervention (risk ratio = 0.38, 95% CI 0.16-0.87, I2 = 0) in patients with hemoptysis. Compared with control, administration of TXA did not cause increased major or minor adverse effects. CONCLUSIONS: TXA provided benefits in terms of a lower short-term mortality rate, less bleeding time, shorter length of hospital stays, and less need for intervention in patients with hemoptysis. Use of TXA was not associated with increased adverse effects.


Assuntos
Antifibrinolíticos/administração & dosagem , Hemoptise/tratamento farmacológico , Mortalidade Hospitalar , Ácido Tranexâmico/administração & dosagem , Antifibrinolíticos/efeitos adversos , Tempo de Sangramento , Hemoptise/mortalidade , Humanos , Tempo de Internação/estatística & dados numéricos , Metanálise como Assunto , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Ácido Tranexâmico/efeitos adversos , Resultado do Tratamento
7.
Neurosci Lett ; 753: 135865, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33812929

RESUMO

Parkinson disease (PD) is a progressive movement functionality disorder resulting in tremor and inability to execute voluntary functions combined with the preponderant non-motor disturbances encompassing constipation and gastrointestinal irritation. Despite continued research, the pathogenesis of PD is not yet clear. The available class of drugs for effective symptomatic management of PD includes a combination of levodopa and carbidopa. In recent past, the link between gut with PD has been explored. According to recent preclinical evidence, pathogens such as virus or bacterium may initiate entry into the gut via the nasal cavity that may aggravate lewy pathology in the gut that eventually propagates and progresses towards the brain via the vagus nerve resulting in the prodromal non-motor symptoms. Additionally, experimental evidence also suggests that alpha-synuclein misfolding commences at a very early stage in the gut and is transported via the vagus nerve prior to seeding PD pathology in the brain. However, this progression and resultant deterioration of the neurones can effectively be altered by an autophagy inducer, Trehalose, although the mechanism behind it is still enigmatic. Hence, this review will mainly focus on analysing the basic components of the gut that might be responsible for aggravating lewy pathology, the mediator(s) responsible for transmission of PD pathology from gut to brain and the important role of trehalose in ameliorating gut dysbiosis related PD complications that would eventually pave the way for therapeutic management of PD.


Assuntos
Autofagia , Encéfalo/patologia , Disbiose/complicações , Microbioma Gastrointestinal/fisiologia , Doença de Parkinson/metabolismo , Animais , Modelos Animais de Doenças , Disbiose/metabolismo , Disbiose/microbiologia , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Doença de Parkinson/microbiologia , Doença de Parkinson/patologia , Agregados Proteicos , Trealose/metabolismo , alfa-Sinucleína/metabolismo
8.
J Agric Food Chem ; 69(16): 4697-4707, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33852294

RESUMO

Platelets play a crucial role in cardiovascular disorders (CVDs); thus, development of a therapeutic target that prevents platelet activation reduces CVDs. Pterostilbene (PTE) has several remarkable pharmacological activities, including anticancer and neuroprotection. Herein, we examined the inhibitory mechanisms of PTE in human platelets and its role in the prevention of vascular thrombosis in mice. At very low concentrations (1-5 µmol/L), PTE strongly inhibited collagen-induced platelet aggregation, but it did not have significant effects against thrombin and 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin (U46619). PTE markedly reduced P-selectin expression on isolated α-granules by a novel microchip. Moreover, PTE inhibited adenosine triphosphate (ATP) release, intracellular ([Ca2+]i) mobilization (resting, 216.6 ± 14.0 nmol/L; collagen-activated platelets, 396.5 ± 25.7 nmol/L; 2.5 µmol/L PTE, 259.4 ± 8.8 nmol/L; 5 µmol/L PTE, 231.8 ± 9.7 nmol/L), phospholipase C (PLC)γ2/protein kinase C (PKC), Akt, and mitogen-activated protein kinase (MAPK) phosphorylation. Neither 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536) nor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reversed platelet aggregation inhibited by PTE. PTE did not affect vasodilator-stimulated phosphoprotein phosphorylation. In mice, PTE obviously reduced the mortality (from 100 to 37.5%) associated with acute pulmonary thromboembolism without increasing the bleeding time. Thus, PTE could be used to prevent CVDs.


Assuntos
Ativação Plaquetária , Trombose , Animais , Plaquetas , Humanos , Camundongos , Fosforilação , Agregação Plaquetária , Resveratrol , Estilbenos , Trombose/prevenção & controle
9.
Autophagy ; : 1-18, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33749503

RESUMO

Basal macroautophagy/autophagy has recently been found in anucleate platelets. Platelet autophagy is involved in platelet activation and thrombus formation. However, the mechanism underlying autophagy in anucleate platelets require further clarification. Our data revealed that LC3-II formation and SQSTM1/p62 degradation were noted in H2O2-activated human platelets, which could be blocked by 3-methyladenine and bafilomycin A1, indicating that platelet activation may cause platelet autophagy. AMPK phosphorylation and MTOR dephosphorylation were also detected, and block of AMPK activity by the AMPK inhibitor dorsomorphin reversed SQSTM1 degradation and LC3-II formation. Moreover, autophagosome formation was observed through transmission electron microscopy and deconvolution microscopy. These findings suggest that platelet autophagy was induced partly through the AMPK-MTOR pathway. In addition, increased LC3-II expression occurred only in H2O2-treated Atg5f/f platelets, but not in H2O2-treated atg5-/- platelets, suggesting that platelet autophagy occurs during platelet activation. atg5-/- platelets also exhibited a lower aggregation in response to agonists, and platelet-specific atg5-/- mice exhibited delayed thrombus formation in mesenteric microvessles and decreased mortality rate due to pulmonary thrombosis. Notably, metabolic analysis revealed that sphingolipid metabolism is involved in platelet activation, as evidenced by observed several altered metabolites, which could be reversed by dorsomorphin. Therefore, platelet autophagy and platelet activation are positively correlated, partly through the interconnected network of sphingolipid metabolism. In conclusion, this study for the first time demonstrated that AMPK-MTOR signaling could regulate platelet autophagy. A novel linkage between AMPK-MTOR and sphingolipid metabolism in anucleate platelet autophagy was also identified: platelet autophagy and platelet activation are positively correlated.Abbreviations: 3-MA: 3-methyladenine; A.C.D.: citric acid/sod. citrate/glucose; ADP: adenosine diphosphate; AKT: AKT serine/threonine kinase; AMPK: AMP-activated protein kinase; ANOVA: analysis of variance; ATG: autophagy-related; B4GALT/LacCS: beta-1,4-galactosyltransferase; Baf-A1: bafilomycin A1; BECN1: beclin 1; BHT: butylate hydrooxytoluene; BSA: bovine serum albumin; DAG: diacylglycerol; ECL: enhanced chemiluminescence; EDTA: ethylenediamine tetraacetic acid; ELISA: enzyme-linked immunosorbent assay; GALC/GCDase: galactosylceramidase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA/GluSDase: glucosylceramidase beta; GPI: glycosylphosphatidylinositol; H2O2: hydrogen peroxide; HMDB: human metabolome database; HRP: horseradish peroxidase; IF: immunofluorescence; IgG: immunoglobulin G; KEGG: Kyoto Encyclopedia of Genes and Genomes; LAMP1: lysosomal associated membrane protein 1; LC-MS/MS: liquid chromatography-tandem mass spectrometry; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MPV: mean platelet volume; MTOR: mechanistic target of rapamycin kinase; ox-LDL: oxidized low-density lipoprotein; pAb: polyclonal antibody; PC: phosphatidylcholine; PCR: polymerase chain reaction; PI3K: phosphoinositide 3-kinase; PLS-DA: partial least-squares discriminant analysis; PRP: platelet-rich plasma; Q-TOF: quadrupole-time of flight; RBC: red blood cell; ROS: reactive oxygen species; RPS6KB/p70S6K: ribosomal protein S6 kinase B; SDS: sodium dodecyl sulfate; S.E.M.: standard error of the mean; SEM: scanning electron microscopy; SGMS: sphingomyelin synthase; SM: sphingomyelin; SMPD/SMase: sphingomyelin phosphodiesterase; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; UGT8/CGT: UDP glycosyltransferase 8; UGCG/GCS: UDP-glucose ceramide glucosyltransferase; ULK1: unc-51 like autophagy activating kinase 1; UPLC: ultra-performance liquid chromatography; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PtdIns3P: phosphatidylinositol-3-phosphate; WBC: white blood cell; WT: wild type.

10.
Neurosci Lett ; 750: 135769, 2021 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-33636285

RESUMO

Continual strategies to devise a complete therapeutic cure for neurodegenerative conditions has been a challenge, majorly due to the presence of blood brain barrier. Lack of targeted delivery in order to minimize loss of dopamine (DA) neurones has been a major challenge to overcome anomalies in Parkinson Disease (PD). PD is a neuromotor degenerative disorder deteriorating motor coordination in affected individuals. Recent research has highlighted the use of lentiviral vectors (LVs) for selective delivery of neuroprotective substance for complete halt of disease progression in PD. LVs have the ability to infect both dividing and non-dividing cells along with non-encoding capability of viral protein that might elicit an immune response. This review will mainly focus on understanding the basic mechanism of action of LVs and its therapeutic aid in PD.


Assuntos
Terapia Genética/métodos , Lentivirus/genética , Doença de Parkinson/terapia , Transfecção/métodos , Animais , Humanos , Doença de Parkinson/genética
11.
Medicine (Baltimore) ; 99(46): e23279, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181719

RESUMO

BACKGROUND: Magnesium sulfate (MgSO4) is widely used in analgesia for different conditions. Recent randomized controlled trials (RCTs) have evaluated the effects of MgSO4 on renal colic; however, this new evidence has not been synthesized. Thus, we conducted a systematic review and meta-analysis to assess the efficacy and safety of MgSO4 in comparison with control for renal colic. METHODS: PubMed, EMBASE, and Scopus databases were searched from inception to February 2020. We included RCTs that evaluated MgSO4 vs control for patients with renal colic. Data were independently extracted by 2 reviewers and synthesized using a random-effects model. RESULTS: Four studies with a total of 373 patients were analyzed. Intravenous MgSO4 15 to 50 mg/kg did not significantly reduce renal colic pain severity at 15 minutes (mean difference [MD] = 0.35, 95% confidence interval [CI] -0.51 to 1.21; 2 RCTs), 30 minutes (MD = 0.19, 95% CI -0.74 to 1.13; 4 RCTs), and 60 minutes (MD = -0.28, 95% CI -0.72 to 0.16; 3 RCTs) in comparison with controls. In patients who failed to respond to initial analgesics, intravenous MgSO4 15 mg/kg or 2 ml of 50% solution provided similar pain relief to ketorolac or morphine at 30 minutes (P = .90) and 60 minutes (P = .57). No significant hemodynamic changes were observed with short-term use of MgSO4 in these studies. CONCLUSION: MgSO4 provides no superior therapeutic benefits in comparison with control treatments. MgSO4 may be used as a rescue medication in patients not responding to initial analgesics. The short-term use of MgSO4 did not affect hemodynamic values.


Assuntos
Sulfato de Magnésio/normas , Manejo da Dor/normas , Cólica Renal/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/normas , Analgésicos/uso terapêutico , Humanos , Sulfato de Magnésio/farmacologia , Sulfato de Magnésio/uso terapêutico , Manejo da Dor/métodos , Manejo da Dor/estatística & dados numéricos
13.
Elife ; 92020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32589144

RESUMO

Traumatic brain injury (TBI) causes mortality and disability worldwide. It can initiate acute cell death followed by secondary injury induced by microglial activation, oxidative stress, inflammation and autophagy in brain tissue, resulting in cognitive and behavioral deficits. We evaluated a new pomalidomide (Pom) analog, 3,6'-dithioPom (DP), and Pom as immunomodulatory agents to mitigate TBI-induced cell death, neuroinflammation, astrogliosis and behavioral impairments in rats challenged with controlled cortical impact TBI. Both agents significantly reduced the injury contusion volume and degenerating neuron number evaluated histochemically and by MRI at 24 hr and 7 days, with a therapeutic window of 5 hr post-injury. TBI-induced upregulated markers of microglial activation, astrogliosis and the expression of pro-inflammatory cytokines, iNOS, COX-2, and autophagy-associated proteins were suppressed, leading to an amelioration of behavioral deficits with DP providing greater efficacy. Complementary animal and cellular studies demonstrated DP and Pom mediated reductions in markers of neuroinflammation and α-synuclein-induced toxicity.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Encefalite/tratamento farmacológico , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Talidomida/análogos & derivados , Animais , Citocinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
14.
Biomed Pharmacother ; 127: 110145, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32361164

RESUMO

Parkinson disease (PD) is the second common neurodegenerative disorder after Alzheimer's disease (AD). The predominant pathological hallmark is progressive loss of dopaminergic (DA) neurones in the substantia nigra (SN) complicated by aggregation of misfolded forms of alpha-synuclein (α-syn). α-syn is a cytosolic synaptic protein localized in the presynaptic neuron under normal circumstances. What drives misfolding of this protein is largely unknown. However, recent studies suggest that autophagy might be an important risk factor for contributing towards PD. Autophagy is an evolutionarily conserved mechanism that causes the clearance or degradation of misfolded, mutated and damaged proteins, organelles etc. However, in an aging individual this process might deteriorate which could possibly lead to the accumulation of damaged proteins. Hence, autophagy modulation might provide some interesting cues for the treatment of PD. Additionally, Fibroblast growth factor 21 (FGF21) which is known for its role as a potent regulator of glucose and energy metabolism has also proved to be neuroprotective in various neurodegenerative conditions possibly via mediation of autophagy.


Assuntos
Autofagia/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Doença de Parkinson/etiologia , Fator 4 Ativador da Transcrição/fisiologia , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/fisiologia , Doença de Parkinson/patologia , Fatores de Transcrição/fisiologia
15.
16.
Nanotechnology ; 31(27): 275204, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32208372

RESUMO

A new flexible memory element is crucial for mobile and wearable electronics. A new concept for memory operation and innovative device structure with new materials is certainly required to address the bottleneck of memory applications now and in the future. We report a new nonvolatile molecular memory with a new operating mechanism based on two-dimensional (2D) material nanochannel field-effect transistors (FETs). The smallest channel length for our 2D material nanochannel FETs was approximately 30 nm. The modified molecular configuration for charge induced in the nanochannel of the MoS2 FET can be tuned by applying an up-gate voltage pulse, which can vary the channel conductance to exhibit memory states. Through controlling the amounts of triggered molecules through either different gate voltage pulses or gate duration time, multilevel states were obtained in the molecular memory. These new molecular memory transistors exhibited an erase/program ratio of more than three orders of current magnitude and high sensitivity, of a few picoamperes, at the current level. Reproducible operation and four-level states with stable retention and endurance were achieved. We believe this prototype device has potential for use in future memory devices.

17.
Eval Program Plann ; 80: 101780, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32044113

RESUMO

Corporate fraud risk management strategy has increasingly become a sustainable business development goal. Recent reforms in forensic accounting technology for corporate fraud risk management globally have opened up new avenues for corporate governance and internal control mechanism implementation. This study thus presents an integrated methodology for forensic accounting implementation to improve the identification of the strategy map relationship between the Balanced Scorecard (BSC)-based perspective and criteria, by combining multiple-criteria decision making (MCDM) with the Decision Making Trial and Evaluation Laboratory (DEMATEL) and the Analytic Network Process (ANP) techniques. The results have implications for corporate decision-makers to effectively fulfil corporate governance quality assurance and anti-fraud through a forensic accounting strategy map illustration. From the evaluation and planning perspective, the in-depth analysis of strategy map is useful to obtain an interrelationship that takes as its starting point the practice professions of the decision maker to improve existing strategy alternatives and focus on the valuable strategy paths. In the evaluation planning application, a strategy map of forensic accounting presents the knowledge regarding key indicators' priorities to achieve satisfactory strategy planning and to practice forensic accounting development linked to fraud risk management in Taiwan.

18.
Cell Rep ; 30(4): 959-968.e3, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31995766

RESUMO

In the adult brain, new dentate granule cells integrate into neural circuits and participate in hippocampal functioning. However, when and how they initiate this integration remain poorly understood. Using retroviral and live-imaging methods, we find that new neurons undergo neurite remodeling for competitive horizontal-to-radial repositioning in the dentate gyrus prior to circuit integration. Gene expression profiling, lipidomics analysis, and molecular interrogation of new neurons during this period reveal a rapid activation of sphingolipid signaling mediated by sphingosine-1-phosphate receptor 1. Genetic manipulation of this G protein-coupled receptor reveals its requirement for successful repositioning of new neurons. This receptor is also activated by hippocampus-engaged behaviors, which enhances repositioning efficiency. These findings reveal that activity-dependent sphingolipid signaling regulates cellular repositioning of new dentate granule cells. The competitive horizontal-to-radial repositioning of new neurons may provide a gating strategy in the adult brain to limit the integration of new neurons into pre-existing circuits.


Assuntos
Giro Denteado/metabolismo , Hipocampo/metabolismo , Neurogênese/genética , Neurônios/metabolismo , Esfingolipídeos/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Animais , Giro Denteado/citologia , Giro Denteado/crescimento & desenvolvimento , Giro Denteado/fisiologia , Feminino , Técnicas de Silenciamento de Genes , Hipocampo/citologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiologia , Lipidômica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/fisiologia , Neurônios/fisiologia , RNA-Seq , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Esfingolipídeos/genética , Receptores de Esfingosina-1-Fosfato/genética
19.
Int J Mol Sci ; 20(20)2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31614900

RESUMO

Thrombin is an essential procoagulant and profibrotic mediator. However, its implication in tuberculous pleural effusion (TBPE) remains unknown. The effusion thrombin and plasminogen activator inhibitor-1 (PAI-1) levels were measured among transudative pleural effusion (TPE, n = 22) and TBPE (n = 24) patients. Pleural fibrosis, identified as radiological residual pleural thickening (RPT) and shadowing, was measured at 12-month follow-up. Moreover, in vivo and in vitro effects of thrombin on PAI-1 expression and mesothelial-mesenchymal transition (MMT) were assessed. We demonstrated the effusion thrombin levels were significantly higher in TBPE than TPE, especially greater in TBPE patients with RPT > 10mm than those without, and correlated positively with PAI-1 and pleural fibrosis area. In carbon black/bleomycin-treated mice, knockdown of protease-activated receptor-1 (PAR-1) markedly downregulated α-smooth muscle actin (α-SMA) and fibronectin, and attenuated pleural fibrosis. In pleural mesothelial cells (PMCs), thrombin concentration-dependently increased PAI-1, α-SMA, and collagen I expression. Specifically, Mycobacterium tuberculosis H37Ra (MTBRa) induced thrombin production by PMCs via upregulating tissue factor and prothrombin, and PAR-1 silencing considerably abrogated MTBRa-stimulated PAI-1 expression and MMT. Consistently, prothrombin/PAR-1 expression was evident in the pleural mesothelium of TBPE patients. Conclusively, thrombin upregulates PAI-1 and MMT and may contribute to tuberculous pleural fibrosis. Thrombin/PAR-1 inhibition may confer potential therapy for pleural fibrosis.


Assuntos
Inibidor 1 de Ativador de Plasminogênio/metabolismo , Pleura/patologia , Receptor PAR-1/metabolismo , Trombina/metabolismo , Tuberculose/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Modelos Animais de Doenças , Exsudatos e Transudatos/metabolismo , Feminino , Fibrose , Seguimentos , Humanos , Masculino , Mesoderma/efeitos dos fármacos , Mesoderma/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mycobacterium tuberculosis/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Derrame Pleural/metabolismo , Derrame Pleural/patologia , Transdução de Sinais , Tuberculose/patologia , Adulto Jovem
20.
Front Neurosci ; 13: 635, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275109

RESUMO

Schizophrenia is a complex and serious mental disorder, and patients with schizophrenia are characterized by psychological hallucinations, deregulated emotionality, and cognitive impairment. Evidence indicated that postnatal neurogenesis in the hippocampus is profoundly impaired in schizophrenic individuals but the role of such dysregulated neurodevelopmental processing in the pathophysiological progress of schizophrenia has not been well investigated. Here in this study, by using the rodent model of schizophrenia through maternal immune activation of poly (I:C) injection, we aimed to examine whether the postnatal neurogenesis might be involved in the development of schizophrenia-like pathology. Through the comprehensive behavioral analyses of multiple core symptoms of schizophrenia at different developmental stages (6-, 9-, and 12-weeks after birth) of the affected offspring, we found a delayed onset of schizophrenia-like behaviors in poly (I:C) animals through the development. Meanwhile, there is an age-dependent alteration of postnatal neurogenesis in the poly (I:C) animals along different development stages by which the aberrant dendritic elaboration functionally correlated with the schizophrenia-like symptoms in 9-week-old of age for the animals. Interestingly, increase in the neurogenesis during a critical period of neurodevelopment exacerbates the schizophrenia-like pathology. Conversely, temporal suppression of aberrant postnatal neurogenesis during the same period of neurodevelopment ameliorates the occurrence of schizophrenia-like symptoms. Together, these findings strongly suggested the aberrant dendritic growth of postnatal neurogenesis during the critical time window of development is essential for controlling the pathophysiological progression of schizophrenia-like symptoms. And pharmacological treatments that adjust these abnormalities may provide potential therapeutic benefits toward patients with schizophrenia in clinic.

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