RESUMO
Artificial grammar learning (AGL) is an experimental paradigm frequently adopted to investigate the unconscious and conscious learning and application of linguistic knowledge. This paper will introduce ENIGMA ( https://enigma-lang.org ) as a free, flexible, and lightweight Web-based tool for running online AGL experiments. The application is optimized for desktop and mobile devices with a user-friendly interface, which can present visual and aural stimuli and elicit judgment responses with RT measures. Without limits in time and space, ENIGMA could help collect more data from participants with diverse personal and language backgrounds and variable cognitive skills. Such data are essential to explain complex factors influencing learners' performance in AGL experiments and answer various research questions regarding L1/L2 acquisition. The introduction of the core features in ENIGMA is followed by an example study that partially replicated Chen (Lang Acquis 27(3):331-361, 2020) to illustrate possible experimental designs and examine the quality of the collected data.
Assuntos
Aprendizagem , Humanos , Psicolinguística , Linguística , Internet , Idioma , MultilinguismoRESUMO
BACKGROUND: Desflurane and sevoflurane are commonly used during inhalational anaesthesia, but few studies have investigated their effects on deep cerebral neuronal activity. In addition, the association between subthalamic nucleus (STN) neurophysiology and general anaesthesia induced by volatile anaesthetics are not yet identified. This study aimed to identify differences in neurophysiological characteristics of the STN during comparable minimal alveolar concentration (MAC) desflurane and sevoflurane anaesthesia for deep brain stimulation (DBS) in patients with Parkinson's disease. METHODS: Twelve patients with similar Parkinson's disease severity received desflurane (n=6) or sevoflurane (n=6) during DBS surgery. We obtained STN spike firing using microelectrode recording at 0.5-0.6 MAC and compared firing rate, power spectral density, and coherence. RESULTS: Neuronal firing rate was lower with desflurane (47.4 [26.7] Hz) than with sevoflurane (63.9 [36.5] Hz) anaesthesia (P<0.001). Sevoï¬urane entrained greater gamma oscillation power than desflurane (62.9% [0.9%] vs 57.0% [1.5%], respectively; P=0.002). There was greater coherence in the theta band of the desflurane group compared with the sevoflurane group (13% vs 6%, respectively). Anaesthetic choice did not differentially influence STN mapping accuracy or the clinical outcome of DBS electrode implantation. CONCLUSIONS: Desflurane and sevoflurane produced distinct neurophysiological profiles in humans that may be associated with their analgesic and hypnotic actions.
Assuntos
Anestésicos Inalatórios/administração & dosagem , Ondas Encefálicas/efeitos dos fármacos , Desflurano/administração & dosagem , Doença de Parkinson/terapia , Sevoflurano/administração & dosagem , Núcleo Subtalâmico/efeitos dos fármacos , Adulto , Idoso , Estimulação Encefálica Profunda , Eletroencefalografia , Feminino , Humanos , Monitorização Neurofisiológica Intraoperatória , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: Tzu Chi University in Taiwan offers a unique mentoring program. This program differs from others as it comprises triple mentorship, namely, faculty mentors, Tzu Cheng/Yi De (TC/YD; senior volunteers), and school counselors. This study aimed to survey the role functions of the mentors from the perspective of medical students. METHODS: The Role Functions of the Mentoring Program Scale (RFMPS) was developed on the basis of literature reviews and focus groups and it underwent exploratory factor analysis for internal consistency and reliability. RFMPS comprises four role functions, namely, mental, educational, career, and humanistic/moral guidance counseling. The survey was distributed to 171 medical students via an online network with two-month intervals and was analyzed using multivariate analysis of variance. RESULTS: The overall response rate was 64% (116/171). The mean scores of the four role functions in descending order belonged to faculty mentors, TC/YD, and school counselors. For humanistic/moral guidance, students had an equal preference for the faculty mentors and TC/YD over school counselors. As for educational, career, and mental guidance counseling, students preferred faculty mentors over TC/YD and school counselors. Faculty mentors provided students with the required guidance counseling for all the four role functions, especially educational guidance; TC/YD in particular offered prominent humanistic/moral guidance and career counseling; school counselors were less preferred but guided students in need. CONCLUSIONS: Medical students value different role functions provided by faculty mentors, TC/YD, and school counselors. A diversified focus could be provided by the faculty mentors, particularly in educational, career, mental, and humanistic/moral counseling; TC/YD specialized in humanistic/moral guidance; and the school counselors carried out their role function only when needed. Humanistic/moral guidance is equally preferred to other types of guidance, which can be equally valuable in future mentoring programs.
Assuntos
Tutoria , Estudantes de Medicina , Humanos , Mentores , Reprodutibilidade dos Testes , Faculdades de Medicina , TaiwanRESUMO
BACKGROUND: General anesthetics-induced changes of electrical oscillations in the basal ganglia may render the identification of the stimulation targets difficult. The authors hypothesized that while sevoflurane anesthesia entrains coherent lower frequency oscillations, it does not affect the identification of the subthalamic nucleus and clinical outcome. METHODS: A cohort of 19 patients with Parkinson's disease with comparable disability underwent placement of electrodes under either sevoflurane general anesthesia (n = 10) or local anesthesia (n = 9). Microelectrode recordings during targeting were compared for neuronal spiking characteristics and oscillatory dynamics. Clinical outcomes were compared at 5-yr follow-up. RESULTS: Under sevoflurane anesthesia, subbeta frequency oscillations predominated (general vs. local anesthesia, mean ± SD; delta: 13 ± 7.3% vs. 7.8 ± 4.8%; theta: 8.4 ± 4.1% vs. 3.9 ± 1.6%; alpha: 8.1 ± 4.1% vs. 4.8 ± 1.5%; all P < 0.001). In addition, distinct dorsolateral beta and ventromedial gamma oscillations were detected in the subthalamic nucleus solely in awake surgery (mean ± SD; dorsal vs. ventral beta band power: 20.5 ± 6.6% vs. 15.4 ± 4.3%; P < 0.001). Firing properties of subthalamic neurons did not show significant difference between groups. Clinical outcomes with regard to improvement in motor and psychiatric symptoms and adverse effects were comparable for both groups. Tract numbers of microelectrode recording, active contact coordinates, and stimulation parameters were also equivalent. CONCLUSIONS: Sevoflurane general anesthesia decreased beta-frequency oscillations by inducing coherent lower frequency oscillations, comparable to the pattern seen in the scalp electroencephalogram. Nevertheless, sevoflurane-induced changes in electrical activity patterns did not reduce electrode placement accuracy and clinical effect. These observations suggest that microelectrode-guided deep brain stimulation under sevoflurane anesthesia is a feasible clinical option.
Assuntos
Anestésicos Inalatórios/administração & dosagem , Estimulação Encefálica Profunda/métodos , Neurônios/efeitos dos fármacos , Doença de Parkinson/terapia , Sevoflurano/administração & dosagem , Núcleo Subtalâmico/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Adulto , Idoso , Anestésicos Locais/administração & dosagem , Ritmo beta/efeitos dos fármacos , Ritmo beta/fisiologia , Estudos de Coortes , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/fisiologia , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/fisiologia , Resultado do TratamentoRESUMO
We investigated effects of magnesium sulfate (MgSO4) on modulating lipopolysaccharide (LPS)-macrophage binding and cluster of differentiation 14 (CD14) expression. Flow cytometry data revealed that the mean levels of LPS-macrophage binding and membrane-bound CD14 expression (mCD14) in differentiated THP-1 cells (a human monocytic cell line) treated with LPS plus MgSO4 (the LPS + M group) decreased by 28.2% and 25.3% compared with those THP-1 cells treated with LPS only (the LPS group) (P < 0.001 and P = 0.037), indicating that MgSO4 significantly inhibits LPS-macrophage binding and mCD14 expression. Notably, these effects of MgSO4 were counteracted by L-type calcium channel activation. Moreover, the mean level of soluble CD14 (sCD14; proteolytic cleavage product of CD14) in the LPS + M group was 25.6% higher than in the LPS group (P < 0.001), indicating that MgSO4 significantly enhances CD14 proteolytic cleavage. Of note, serine protease inhibition mitigated effects of MgSO4 on both decreasing mCD14 and increasing sCD14. In conclusion, MgSO4 inhibits LPS-macrophage binding through reducing CD14 expression. The mechanisms may involve antagonizing L-type calcium channels and activating serine proteases.
Assuntos
Receptores de Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Sulfato de Magnésio/farmacologia , Células THP-1/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Células THP-1/metabolismoRESUMO
BACKGROUND: Nod-like receptor protein 3 (NLRP3) inflammasome is a multiprotein complex composed of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain. Activation of NLRP3 inflammasome leads to interleukin-1ß (IL-1ß) upregulation and pyroptosis, a proinflammatory cell death characterized by increased cell size. Of note, calcium signaling is crucial for NLRP3 inflammasome activation. This study elucidated the effects of magnesium sulfate (MgSO4), a potent calcium antagonist, on modulating NLRP3 inflammasome. MATERIALS AND METHODS: THP-1 cells, the human monocytic leukemia cell line, were treated with lipopolysaccharide (LPS, 1 µg/ml) plus nigericin (5 µM) (the LPS + Nig group) and LPS plus nigericin plus MgSO4 (20 mM) [the LPS + Nig + M(20)] to facilitate investigations. Levels of IL-1ß, pyroptosis, and NLRP3 inflammasome induction as well as intracellular calcium were assayed. RESULTS: IL-1ß concentration of the LPS + Nig + M(20) group was significantly lower than the LPS + Nig group (P = 0.001). Cell size of the LPS + Nig + M(20) group was significantly smaller than the LPS + Nig group (P < 0.001). Level of pyroptotic cell death of the LPS + Nig + M(20) group was significantly lower than the LPS + Nig group (P = 0.004). NLRP3 mRNA and protein concentrations of the LPS + Nig + M(20) group were also significantly lower than the LPS + Nig group (P = 0.021 and P < 0.001). Similarly, apoptosis-associated speck-like protein containing a caspase recruitment domain speck formation ratio and caspase-1 concentration of the LPS + Nig + M(20) group were significantly lower than the LPS + Nig group (both P < 0.001). The change in intracellular calcium level of the LPS + Nig + M(20) group was significantly smaller than the LPS + Nig group (P = 0.001). CONCLUSIONS: MgSO4 inhibits NLRP3 inflammasome, IL-1ß upregulation, and pyroptosis. The mechanism is consistent with decreased intracellular calcium levels.
Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Inflamassomos/antagonistas & inibidores , Sulfato de Magnésio/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/efeitos dos fármacos , Caspase 1/metabolismo , Domínio de Ativação e Recrutamento de Caspases , Humanos , Interleucina-1beta/metabolismo , Células THP-1RESUMO
We explored whether the combination of anti-oxidant and anti-inflammatory guava (Psidium guajava) and trehalose treatment protects the kidney and pancreas against Type II diabetes (T2DM)-induced injury in rats. We measured the active component of guava juice by HPLC analysis. T2DM was induced in Wistar rats by intraperitoneal administration of nicotinamide and streptozotocin and combination with high fructose diets for 8 weeks. The rats fed with different dosages of guava juice in combination with or without trehalose for 4 weeks were evaluated the parameters including OGTT, plasma insulin, HbA1c, HOMA-IR (insulin resistance) and HOMA-ß (ß cell function and insulin secretion). We measured oxidative and inflammatory degrees by immunohistochemistry stain, fluorescent stain, and western blot and serum and kidney reactive oxygen species (ROS) by a chemiluminescence analyzer. High content of quercetin in the guava juice scavenged H2O2 and HOCl, whereas trehalose selectively reduced H2O2, not HOCl. T2DM affected the levels in OGTT, plasma insulin, HbA1c, HOMA-IR and HOMA-ß, whereas these T2DM-altered parameters, except HbA1c, were significantly improved by guava and trehalose treatment. The levels of T2DM-enhanced renal ROS, 4-hydroxynonenal, caspase-3/apoptosis, LC3-B/autophagy and IL-1ß/pyroptosis were significantly decreased by guava juice and trehalose. The combination with trehalose and guava juice protects the pancreas and kidney against T2DM-induced injury.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Psidium/química , Piroptose/efeitos dos fármacos , Trealose/farmacologia , Animais , Biomarcadores , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Imuno-Histoquímica , Insulina/sangue , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Quercetina/química , Ratos , Espécies Reativas de Oxigênio/químicaRESUMO
Recent evidence shows that the NMDAR postsynaptic density-95 (PSD-95), growth-associated protein-43 (GAP-43), and matrix metalloproteinase-9 (MMP-9) protein enhance neuroplasticity at the subacute stage of stroke. Here, we evaluated whether melatonin would modulate the PSD-95, GAP-43, and MMP-9 proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to experimental stroke. Adult male Sprague-Dawley rats were treated with melatonin (5 mg/kg) or vehicle at reperfusion onset after transient occlusion of the right middle cerebral artery (tMCAO) for 90 min. Animals were euthanized for Western immunoblot analyses for the PSD-95 and GAP-43 proteins and gelatin zymography for the MMP-9 activity at 7 days postinsult. Another set of animals was sacrificed for histologic and Golgi-Cox-impregnated sections at 28 days postinsult. In cultured neurons exposed to glutamate excitotoxicity, melatonin significantly upregulated the GAP-43 and PSD-95 expressions and improved dendritic aborizations (P<0.05, respectively). Relative to controls, melatonin-treated stroke animals caused a significant improvement in GAP-43 and PSD-95 expressions as well as the MMP-9 activity in the ischemic brain (P<0.05). Consequently, melatonin also significantly promoted the dendritic spine density and reduced infarction in the ischemic brain, and improved neurobehaviors as well at 28 days postinsult (P<0.05, respectively). Together, melatonin upregulates GAP-43, PSD-95, and MMP-9 proteins, which likely accounts for its actions to improve neuroplasticity in cultured neurons exposed to glutamate excitotoxicity and to enhance long-term neuroprotection, neuroplasticity, and brain remodeling in stroke rats.
Assuntos
Isquemia Encefálica/metabolismo , Proteína GAP-43/metabolismo , Ácido Glutâmico/toxicidade , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Melatonina/farmacologia , Proteínas de Membrana/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Células Cultivadas , Proteína 4 Homóloga a Disks-Large , Masculino , Neurônios , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
The starting-small effect is a cognitive advantage in language acquisition when learners begin by generalizing on regularities from structurally simple and shorter tokens in a skewed input distribution. Our study explored this effect as a potential explanation for the biased learning of opaque and transparent vowel harmony. In opaque vowel harmony, feature agreement occurs strictly between adjacent vowels, and an intervening "neutral vowel" blocks long-distance vowel harmony. Thus, opaque vowel harmony could be acquired even if learners start with structurally simpler and more frequent disyllabic tokens. Alternatively, transparent vowel harmony can only be observed in longer tokens demonstrating long-distance agreement by skipping a neutral vowel. Opaque vowel harmony is predicted to be learned more efficiently due to its compatibility with local dependency acquired via starting-small learning. In two artificial grammar learning experiments, learners were exposed to both vowel harmony patterns embedded in an equal number of disyllabic and trisyllabic tokens or a skewed distribution with twice as many disyllabic tokens. In Exp I, learners' test performance suggests the consistently biased learning of local and opaque vowel harmony with starting-small learning. Furthermore, in Exp II, the acquired vowel harmony patterns varied significantly by working memory capacity with a balanced but not skewed input distribution, presumably because of the ease of cognitive demand with starting-small learning.
RESUMO
OBJECTIVES: Tracheal intubation is used to maintain a patent airway and can occasionally be difficult in a potentially difficult airway, especially for novice managers. In this study, we evaluated the time required, extent of the difficulty, and number of dental clicks in the tracheal intubation for novice medical students between the Macintosh (Truphatek International Ltd, Netanya, Israel) and 3 video laryngoscopes in normal and difficult simulated intubation positions on manikins on both the table and floor. METHODS: We recruited 20 medical students as novice airway managers. They used the Macintosh, Truview (Truphatek International Ltd, Netanya, Israel), Glidescope (Verathon Inc., Bothell, WA), and Airway Scope (AWS) (Pentax Corporation, Tokyo, Japan) laryngoscopes in normal and difficult simulated airways on manikins on both the table and floor. The time to intubate, modified Cormack-Lehane score, intubation difficulty score, and dental click number were estimated and compared. RESULTS: All 20 medical students completed the study. The AWS required the shortest intubation time, provided the best glottic view and easiest intubation, and resulted in less dental clicks compared with the other 3 laryngoscopes; these phenomena were particularly prominent in the cervical-spine immobilization position on the floor. Although all video laryngoscopes provided better glottic views than the Macintosh laryngoscopy in terms of time to intubate, intubation difficulty score, and the number of dental clicks, the outcomes from the Macintosh laryngoscope were better than those of the Truview and Glidescope. CONCLUSIONS: The AWS may have the potential for quicker, easier, and safer tracheal intubation in scenarios involving difficult airways for a novice airway manager.
Assuntos
Intubação Intratraqueal/instrumentação , Laringoscópios , Competência Clínica , Humanos , Manequins , Estudantes de Medicina , Fatores de Tempo , Gravação em Vídeo/instrumentaçãoRESUMO
Lexical tone identification requires a number of secondary cues, when main tonal contours are unavailable. In this article, we examine Mandarin native speakers' ability to identify lexical tones by extracting tonal information from sonorant onset pitch (onset contours) on syllable-initial nasals ranging from 50 to 70 ms in duration. In experiments I and II we test speakers' ability to identify lexical tones in a second syllable with and without onset contours in isolation (experiment I) and in a sentential context (experiment II). The results indicate that speakers can identify lexical tones with short distinctive onset contour patterns,they also indicate that misperception of tones 213 and 24 are common. Furthermore, in experiment III, we test whether onset contours in a following syllable can be utilized by listeners in tone identification. We find that onset contours in the following syllable also contribute to the identification of the target lexical tones. The conclusions are twofold: (1) Mandarin lexical tones can be identified with onset contours; (2) tonal domain must be extended to include not just typical cues of tones but also coarticulated tonal patterns.
Assuntos
Sinais (Psicologia) , Idioma , Fonética , Percepção da Altura Sonora , Acústica da Fala , Percepção da Fala , HumanosRESUMO
Background: Early mobilization post-total knee arthroplasty (TKA) significantly affects patient outcomes. While parecoxib is known to reduce postoperative pain and morphine use with a favorable safety profile, its impact on mobilization timing post-TKA remains uncertain. This retrospective study aims to assess parecoxib's influence on postoperative mobilization timing in TKA patients without compromising safety. Methods: This study included unilateral TKA patients treated for primary knee osteoarthritis under general anesthesia. We divided the study period into two intervals, 2007-2012 and 2013-2018, to evaluate temporal differences. Both the control group and parecoxib group received standard postoperative oral analgesics and as-needed intramuscular morphine. The control group did not receive parecoxib, while the parecoxib group did. Primary outcomes compared postoperative complications and mobilization timing between groups, with secondary outcomes including length of hospital stay (LOS), Visual Analog Scale (VAS) scores for pain, as-needed morphine use, and postoperative nausea/vomiting. Results: Parecoxib did not increase postoperative complications. Unmatched comparison with patients in controlled group found that patients in parecoxib group had significantly shortened mobilization time (2.2 ± 1.1 vs. 2.7 ± 1.6 days, P < 0.001) and LOS (6.7 ± 2.5 vs. 7.2 ± 2.1 days, P = 0.01). Multivariate analysis linked parecoxib use with faster mobilization (ß = -0.365, P < 0.001) but not LOS. Males showed increased mobilization time and LOS compared to females during the period of 2007-2018, but gender had no significant association with LOS during the period of 2013-2018. The 2013-2018 period saw significant reductions in both mobilization time and LOS. Use of a tourniquet and local infiltration analgesia showed no significant impact. ASA classification 1-2 was positively associated with faster mobilization but not LOS. Longer operation times were linked to delayed mobilization and increased LOS. Conclusion: In this study, intravenous parecoxib injection, female gender, and shorter OP time had consistent positive association with shorter time to mobilization after individual multivariate analysis in 2 different period. The use of parecoxib had consistent no significant association with LOS. Only shorter OP time was consistent positive associated with shorter LOS.
RESUMO
OBJECTIVE: We explored the putative anti-inflammatory effects of nicotinamide against experimental stroke. DESIGN: Prospective laboratory study. SETTING: Research laboratory in a university teaching hospital. SUBJECTS: Adult male Sprague-Dawley rats (250-300 g). INTERVENTIONS: The antioxidant, radical scavenging, and anti-inflammatory actions of nicotinamide were evaluated using a panel of acellular assays and lipopolysaccharide-stimulated RAW 264.7 and BV2 cells. Animals were subjected to transient middle cerebral artery occlusion for 90 mins. Nicotinamide (500 mg/kg) or vehicle was given intravenously at reperfusion onset. MEASUREMENTS AND MAIN RESULTS: Nicotinamide effectively inhibited nuclear factor-κB translocation and binding activity as well as the production of tumor necrosis factor-α, nitrite/nitrate, and interleukin-6 in the lipopolysaccharide-stimulated RAW 264.7 and BV2 cells (p < .05, respectively) but exhibited weak antioxidant and radical-scavenging actions. Relative to controls, nicotinamide-treated animals had significant reductions in neutrophil and macrophage/activated microglial infiltration in the ischemic brain by 53% and 77% (p < .05, respectively). Additionally, nicotinamide significantly attenuated phosphorylation of nuclear factor-κB's inhibitory protein, nuclear factor-κB translocation and binding activity, and the synthesis of inducible nitric oxide in the ischemic brain (p < .05, respectively). Consequently, nicotinamide effectively reduced brain infarction and improved neurobehavioral outcome by 43% and 50% (p < .05, respectively). CONCLUSIONS: Nicotinamide effectively attenuated postischemic nuclear factor-kappa]B activation and exhibited robust anti-inflammatory actions against ischemic stroke.
Assuntos
Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/metabolismo , NF-kappa B/efeitos dos fármacos , Niacinamida/farmacologia , Animais , Comportamento Animal , Intervalos de Confiança , Modelos Animais de Doenças , Eletroforese em Gel Bidimensional , Immunoblotting , Imuno-Histoquímica , Interleucina-6/análise , Interleucina-6/metabolismo , Ataque Isquêmico Transitório/patologia , Peroxidação de Lipídeos/fisiologia , Masculino , NF-kappa B/metabolismo , Peroxidase/análise , Peroxidase/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Valores de Referência , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We sought to determine the optimal Percoll concentration for ischemic rat brain prepared for flow cytometric (FC) measurements. Animals were subjected to the right middle cerebral artery (MCA) occlusion, and were euthanized at 3, 12, 24, and 72 h after reperfusion onset. The brains were processed by different concentrations (unisolated, 20, 25, 30, or 40%) of Percoll and stained with annexin V/propidium iodine (PI). Ischemic brain damage was evaluated by FC analysis and image analysis for histologic sections. The relative susceptibility of different phenotypes of cells to necrotic and apoptotic damage were evaluated by the FC analyses for the immunohistochemistry, PI, and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-processed brain tissues. Our results showed that FC analysis effectively detected the extent and maturation of apoptotic/necrotic brain damage, and the results were consistent with those determined from histologic brain sections. Neuron was more vulnerable to apoptosis than glia, whereas both cellular phenotypes were compatible in susceptibility for necrotic cell death. Percoll at a low concentration (20%) could effectively remove tissue debris without affecting membranous integrity of the injured neurons. Conversely, high percentages of Percoll (30-40%) substantially increased membranous damage for the injured cells. These results supported the application of FC to determine the extent and progression in time, as well as relative phenotypes of apoptotic/necrotic cell deaths following ischemic damage. We highlighted the use of Percoll at low percentages to facilitate the removal of tissue debris and to improve membrane integrity preservation for the injured neurons.
Assuntos
Citometria de Fluxo/métodos , Infarto da Artéria Cerebral Média/patologia , Neuroglia/patologia , Neurônios/patologia , Animais , Anexina A5/química , Apoptose/fisiologia , Modelos Animais de Doenças , Ataque Isquêmico Transitório/patologia , Masculino , Necrose , Neuroglia/metabolismo , Neurônios/metabolismo , Povidona/química , Propídio/química , Ratos , Ratos Sprague-Dawley , Dióxido de Silício/química , Coloração e Rotulagem/métodosRESUMO
We explored anti-inflammatory potential of melatonin against the lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro. RAW 264.7 and BV2 cells were stimulated by LPS, followed by the treatment with melatonin or vehicle at various time intervals. In a mouse model of meningitis induced by LPS, melatonin (5mg/kg) or vehicle was intravenously injected at 30min postinsult. The activity of matrix metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) was determined by gelatin zymography. Nuclear factor-kappa B (NFκB) translocation and binding activity were determined by immunocytochemistry and electrophoretic mobility shift assay (EMSA). Our results showed that either pretreatment or cotreatment with melatonin at 50-500 µm effectively inhibited the LPS-induced proMMP-9 activation in the RAW 264.7 and BV2 cells, respectively (P<0.05). This melatonin-induced proMMP-9 inhibition remained effective when treatment was delayed up to 2 and 6hr postinsult for RAW 264.7 and BV2 cells, respectively (P<0.05 for both groups). Additionally, melatonin significantly attenuated the rises of circulatory and cerebral MMP-9 activity, respectively (P<0.05) and reduced the loss of body weight (P<0.05) in mice with meningitis. Moreover, melatonin (50µm) effectively inhibited nuclear factor-kappa B (NFκB) translocation and binding activity in the LPS-treated RAW 264.7 and BV2 cells, respectively (P<0.05). These results demonstrate direct inhibitory actions of melatonin against postinflammatory NFκB translocation and MMP-9 activation and highlight its ability to inhibit systemic and cerebral MMP-9 activation following brain inflammation.
Assuntos
Lipopolissacarídeos/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Meningite/tratamento farmacológico , Meningite/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Ensaio de Desvio de Mobilidade Eletroforética , Ativação Enzimática/efeitos dos fármacos , Imuno-Histoquímica , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , NF-kappa B/metabolismoRESUMO
INTRODUCTION: Acute respiratory infection (ARI) can significantly reduce postoperative quality of life and impair the recovery of older adult patients with lower-limb fractures, and its relationship with methods of anesthesia remains inconclusive. Using data from the National Health Insurance Research Database (NHIRD) of Taiwan, this study examined the data of patients who received surgical management for lower-limb fractures and compared those who underwent general anesthesia (GA) with those who underwent regional anesthesia (RA) in terms of their incidence of acute upper and lower respiratory infection during the one-month postoperative period. The study also identified related risk factors. MATERIAL AND METHODS: Approximately two million patients were randomly sampled from the NHIRD registry. We identified and enrolled patients with lower-limb fractures who were over 60 years old and underwent GA or RA during surgeries conducted between 2010 and 2017. We divided these patients into two groups for further analysis. The outcome of this study was the development of ARI during the one-month postoperative period. RESULTS: In total, 45,032 patients (GA group, 19,580 patients; RA group, 25,452 patients) with a mean age of 75.0 ± 8.9 years were included in our study. The incidence of postoperative ARI within one month of surgery was 8.0% (1562 patients) in the GA group and 9.5% (2412 patients) in the RA group, revealing a significant difference. The significant risk factors for the incidence of ARI were the application of RA for surgery, older age, hypertension, liver disease, and chronic obstructive pulmonary disease (COPD). A subgroup analysis revealed that the RA method was associated with a significantly higher ARI incidence relative to the GA method among patients aged between 60 and 80 years, among male patients, among the patients with or without any comorbidity and among the patients without COPD. CONCLUSION: The incidence of postoperative ARI within one month of surgery was higher among older patients with lower-limb fractures who received RA for surgery than among those who received GA for surgery. The other major risk factors for ARI were older age, hypertension, liver disease, and COPD. Therefore, we should focus on patients with a high risk of developing ARI, especially during the COVID-19 pandemic.
Assuntos
Raquianestesia , COVID-19 , Fraturas Ósseas , Hipertensão , Traumatismos da Perna , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Raquianestesia/efeitos adversos , Incidência , Qualidade de Vida , Pandemias , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Anestesia Geral/efeitos adversos , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/cirurgia , Extremidade Inferior/cirurgia , Doença Pulmonar Obstrutiva Crônica/etiologia , Hipertensão/complicações , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: We have previously shown that cinnamophilin ([8R, 8'S]-4, 4'-dihydroxy-3, 3'-dimethoxy-7-oxo-8, 8'-neolignan) exhibited potent antioxidant, radical-scavenging, and anti-inflammatory actions and reduced acute ischemic brain damage, even when it was given up to 6 hrs postinsult. Here, we characterized the long-lasting neuroprotection of cinnamophilin against gray and white matter damage and its beneficial effects on electrophysiological and functional outcomes in a model of stroke. DESIGN: Prospective laboratory animal study. SETTING: Research laboratory in a university teaching hospital. SUBJECTS: Adult male Sprague-Dawley rats (240-290 g). INTERVENTIONS: Under controlled conditions of normoxia, normocarbia, and normothermia, spontaneously breathing, halothane-anesthetized (1.0-1.5%) rats were subjected to transient middle cerebral artery occlusion for 90 mins. Cinnamophilin (80 mg/kg) or vehicle was given intravenously at reperfusion onset. MEASUREMENTS AND MAIN RESULTS: Physiological parameters, including arterial blood gases and cortical blood perfusion, somatosensory-evoked potentials, and neurobehavioral outcomes, were serially examined. Animals were euthanized at 7 days or 21 days postinsult. Gray matter and white matter (axonal and myelin) damage were then evaluated by quantitative histopathology and immunohistochemistry against phosphorylated component-H neurofilaments and myelin basic protein, respectively. After the follow-up period of 7 and 21 days, our results showed that cinnamophilin significantly decreased gray matter damage by 31.6% and 34.9% (p < .05, respectively) without notable adverse effects. Additionally, cinnamophilin effectively reduced axonal and myelin damage by 46.3-68.6% (p < .05) and 25.2-28.1% (p < .05), respectively. Furthermore, cinnamophilin not only improved the ipsilateral field potentials (p < .05, respectively), but also reduced the severity of contralateral electrophysiological diaschisis (p < .05). Consequently, cinnamophilin improved sensorimotor outcomes up to 21 days postinsult (p < .05, respectively). CONCLUSIONS: Administration with cinnamophilin provides long-lasting neuroprotection against gray and white matter damage and improves functional and electrophysiological outcomes after ischemic stroke. The results suggest a need for further studies to characterize the potential of cinnamophilin in the field of ischemic stroke.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Guaiacol/análogos & derivados , Ataque Isquêmico Transitório/tratamento farmacológico , Lignanas/farmacologia , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Amielínicas/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Peso Corporal , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Córtex Cerebral/patologia , Intervalos de Confiança , Modelos Animais de Doenças , Eletrofisiologia , Potenciais Somatossensoriais Evocados , Guaiacol/farmacologia , Ataque Isquêmico Transitório/patologia , Ataque Isquêmico Transitório/prevenção & controle , Masculino , Fibras Nervosas Mielinizadas/patologia , Fibras Nervosas Amielínicas/patologia , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Taxa de SobrevidaRESUMO
BACKGROUND: Although the principles of antibiotics prophylaxis are well established, more than 60% of hospitals that joined the international quality indicator project failed to discontinue the use of prophylactic antibiotics within 24h after coronary artery bypass grafting (CABG). Our specific aims are to disseminate the gain obtained from breakthrough series model in knee arthroplasty and abdominal hysterectomy to increase the rate of prophylactic duration not longer than 24h in patients with CABG. METHODS: The control and intervention groups enrolled 55 and 78 patients with CABG before and after the project. Measurements were prophylactic interval and duration, surgical site infection, hospital and antibiotics costs. Two strategies were developed. The key cardiac surgeon was invited to attend quality improvement activities. Knowledge and rationale of medical quality indicators would thus be communicated. Secondly, we proposed a regional symposium in which a level of competition was subconsciously established, and practitioners would present their level of compliance. RESULTS: Instances of prophylactic interval within 1h prior to incision were significantly increased from 66.7% to 97.4%. Rates of prophylactic duration less than 24h were significantly increased from 2.8% to 66.1%. The average hospital cost was reduced by 16.4%, and antibiotics cost was reduced by 91.8%. No significant changes in surgical site infection within 30 d of CABG were observed. CONCLUSIONS: We successfully disseminated the gain of breakthrough project in improving antimicrobial prophylaxis to CABG. By implementing this model, we are able to optimize the timing and duration of antimicrobial prophylaxis in patients with CABG to a level above worldwide average.