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We propose extreme field confinement in a zigzag plasmonic crystal that can produce a wide plasmonic bandgap near the visible frequency range. By applying a periodic zigzag structure to a metal-insulator-metal plasmonic waveguide, the lowest three plasmonic crystal bands are flattened, creating a high-quality broadband plasmonic mirror over a wavelength range of 526-909 nm. Utilizing zigzag plasmonic crystals in a three-dimensional tapered metal-insulator-metal plasmonic cavity, extreme field confinement with a modal volume of less than 0.00005 λ 3 can be achieved even at resonances over a wide frequency range. In addition, by selecting the number of zigzag periods in the plasmonic crystal, critical coupling between the cavity and the waveguide can be achieved, thereby maximizing the field intensity with an enhancement factor of 105 or more. We believe that zigzag plasmonic crystals will provide a powerful platform for implementing broadband on-chip plasmonic devices.
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BACKGROUND: False positive rate (FPR) of the current basic life support (BLS) termination of resuscitation (TOR) rule in out-of-hospital cardiac arrest (OHCA) patients (not witnessed; no return of spontaneous circulation prior to transport; and no shocks were delivered) has been ethically challenging. We validated the current BLS TOR rule with using nationwide Korean Cardiac Arrest Research Consortium (KoCARC) registry and identified the factors for modifying the rules. METHODS: This prospective, multicenter, registry-based study was performed using the nontraumatic OHCA registry data between October 2015 and June 2017. Independent factors associated with poor neurologic outcome were identified to propose new KoCARC TOR rules by using multivariable analysis. The diagnostic performances of the TOR rules were calculated respectively. RESULTS: Among 4,360 OHCA patients, 2,801 (64.2%) satisfied all 3 criteria of the BLS TOR rule. The FPR and positive predictive value of the BLS TOR rule were 5.9% and 99.3%. Asystole as initial rhythm and age >â¯60â¯years were found as new factors for modifying the TOR rule. New KoCARC TOR rules, combination of asystole and age >â¯60â¯years with current TOR rule, showed lower FPR (0.3%-2.1%) and higher positive predictive value (99.7%-99.9%) for predicting poor neurologic outcome at discharge. CONCLUSIONS: In this recent nationwide cohort, the current BLS TOR rule showed high FPR (5.9%) for predicting poor neurologic outcome. We anticipate that our new KoCARC TOR rules, application of 2 new factors (asystole as initial rhythm and age >â¯60â¯years) with BLS TOR rule, could reduce unwarranted death.
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Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario/terapia , Sistema de Registros , Órdenes de Resucitación , Privación de Tratamiento , Factores de Edad , Anciano , Circulación Sanguínea , Reanimación Cardiopulmonar/estadística & datos numéricos , Cardioversión Eléctrica , Reacciones Falso Positivas , Femenino , Paro Cardíaco , Humanos , Masculino , Inutilidad Médica , Persona de Mediana Edad , Análisis Multivariante , Paro Cardíaco Extrahospitalario/etiología , Valor Predictivo de las Pruebas , República de Corea , Resultado del TratamientoRESUMEN
In recent years, novel high-performance nanophotonic devices have been realized by applying ultrathin two-dimensional nanolayer materials to nanophotonics. In this paper, we propose nanolayer-embedded compact pseudo-photonic crystals (PPCs) that enable strong interaction between ultrathin nanolayers and photonic crystal modes. In typical two-dimensional slab photonic crystals, the transverse-magnetic (TM) photonic crystal bandgap is not well formed, making it difficult to operate the TM photonic crystal waveguide modes. However, by utilizing the low-frequency TM PPC bands, a long propagation TM waveguide mode, a slow TM waveguide mode, and a TM photonic bandgap are all readily available. In particular, the insertion of a nanometer-thick low-refractive-index layer in the vertical center of TM PPC waveguide can localize the electric fields tightly in nanometer space, causing strong field interaction with the inserted nanolayer material. Using the TM slow light near PPC band edges, field interaction with the nanolayer is significantly enhanced. We can also realize nanolayer-embedded high-quality-factor (Q-factor > 104) PPC cavities using the TM PPC bandgap. We believe that the proposed TM PPCs will play an important role in the strong interaction of ultrathin nanolayer materials with photonic crystal modes.
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The cytotoxic drugs used in chemotherapy are often accompanied by nausea and vomiting. Despite the use of antiemetic drugs, chemotherapy-induced nausea and vomiting (CINV) remain significant side effects for cancer patients and are associated with serotonin type 3 receptor (5-HT3R) activation in the brainstem. Farnesol and nerolidol are sesquiterpene alcohols found in essential oils of plants such as roses, citronella, and lemon grass and are used as antiemetic parapheromones. Medicinal plants often are effective in treating gastrointestinal disorders, including CINV, although the mechanism of action remains unclear. In the current work, the antiemetic efficacy of the naturally occurring racemic mixture of farnesol (m-farnesol) and nerolidol (m-nerolidol) against cisplatin CINV was tested using the pica behavior (consumption of nonnutritive substances) of rats. Animals treated with m-farnesol or m-nerolidol consumed a smaller amount of kaolin than of saline-treated control animals. This result is consistent with the antiemetic efficacy of farnesol and nerolidol. Compared with controls, m-farnesol- but not m-nerolidol-treated animals consumed more food and lost less body weight. Thus, farnesol effectively reduced appetite suppression and weight loss induced by cisplatin. In separate experiments, isomers of farnesol and nerolidol were tested on 5-HT-induced responses of acutely isolated nodose neurons using patch-clamp methods. All the tested constituents inhibited 5-HT3R-mediated current in a noncompetitive manner. Thus, both farnesol and nerolidol may exert antiemetic efficacy by inhibiting 5-HT signaling in cranial visceral afferents, resulting in interruption of emetogenic signaling; however, nerolidol failed to suppress cisplatin-induced anorexia and weight loss, suggesting that additional mechanisms may contribute.
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Antieméticos/farmacología , Antineoplásicos/efectos adversos , Náusea/tratamiento farmacológico , Vómitos/tratamiento farmacológico , Animales , Apetito/efectos de los fármacos , Cisplatino/efectos adversos , Farnesol/farmacología , Masculino , Náusea/inducido químicamente , Aceites Volátiles/farmacología , Pica/tratamiento farmacológico , Ratas , Ratas Wistar , Receptores de Serotonina 5-HT3/metabolismo , Sesquiterpenos/farmacología , Vómitos/inducido químicamente , Pérdida de Peso/efectos de los fármacosRESUMEN
PR interval is the period from the onset of P wave to the start of the QRS complex on electrocardiograms. A recent genomewide association study (GWAS) suggested that GAREM1 was linked to the PR interval on electrocardiograms. This study was designed to validate this correlation using additional subjects and examined the function of Garem1 in a mouse model. We analyzed the association of rs17744182, a variant in the GAREM1 locus, with the PR interval in 5646 subjects who were recruited from 2 Korean replication sets, Yangpyeong (n = 2471) and Yonsei (n = 3175), and noted a significant genomewide association by meta-analysis (P = 2.39 × 10-8). To confirm the function of Garem1 in mice, Garem1 siRNA was injected into mouse tail veins to reduce the expression of Garem1. Garem1 transcript levels declined by 53% in the atrium of the heart (P = 0.029), and Garem1-siRNA injected mice experienced a significant decrease in PR interval (43.27 ms vs. 44.89 ms in control, P = 0.007). We analyzed the expression pattern of Garem1 in the heart by immunohistology and observed specific expression of Garem1 in intracardiac ganglia. Garem1 was expressed in most neurons of the ganglion, including cholinergic and adrenergic cells. We have provided evidence that GAREM1 is involved in the PR interval of ECGs. These findings increase our understanding of the regulatory signals of heart rhythm through intracardiac ganglia of the autonomic nervous system and can be used to guide the development of a therapeutic target for heart conditions, such as atrial fibrillation.
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Electrocardiografía , Proteína Adaptadora GRB2/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Sistema de Conducción Cardíaco , Adulto , Anciano , Alelos , Animales , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/genética , Fibrilación Atrial/fisiopatología , Línea Celular , Modelos Animales de Enfermedad , Femenino , Proteína Adaptadora GRB2/metabolismo , Expresión Génica , Silenciador del Gen , Variación Genética , Genotipo , Atrios Cardíacos/citología , Atrios Cardíacos/metabolismo , Atrios Cardíacos/fisiopatología , Humanos , Masculino , Ratones , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , ARN Interferente Pequeño/genéticaRESUMEN
We propose a novel design for a sub-5-nm-gap plasmonic cavity to couple it efficiently with an integrated low loss silicon waveguide. We numerically obtain over 90% efficient coupling between a nano-gap plasmonic cavity with a modal volume of less than 10-7λ3 and a conventional silicon-on-insulator (SOI) waveguide by utilizing the anti-symmetric second-order resonance mode of the cavity and engineering its geometry to reduce the modal size to less than 5 nm. The electromagnetic field efficiently coupled to the small cavity, leading to extreme enhancement of the field intensity. For a 2-nm-gap cavity, the intensity enhancement was calculated to be more than 100,000,000 compared to that of light in an SOI waveguide.
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Recent evidence has shown that Ras homolog enriched in brain (Rheb) is dysregulated in Alzheimer's disease (AD) brains. However, it is still unclear whether Rheb activation contributes to the survival and protection of hippocampal neurons in the adult brain. To assess the effects of active Rheb in hippocampal neurons in vivo, we transfected neurons in the cornu ammonis 1 (CA1) region in normal adult rats with an adeno-associated virus containing the constitutively active human Rheb (hRheb(S16H)) and evaluated the effects on thrombin-induced neurotoxicity. Transduction with hRheb(S16H) significantly induced neurotrophic effects in hippocampal neurons through activation of mammalian target of rapamycin complex 1 (mTORC1) without side effects such as long-term potentiation impairment and seizures from the alteration of cytoarchitecture, and the expression of hRheb(S16H) prevented thrombin-induced neurodegeneration in vivo, an effect that was diminished by treatment with specific neutralizing antibodies against brain-derived neurotrophic factor (BDNF). In addition, our results showed that the basal mTORC1 activity might be insufficient to mediate the level of BDNF expression, but hRheb(S16H)-activated mTORC1 stimulated BDNF production in hippocampal neurons. These results suggest that viral vector transduction with hRheb(S16H) may have therapeutic value in the treatment of neurodegenerative diseases such as AD.
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Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Región CA1 Hipocampal/metabolismo , Proteínas de Unión al GTP Monoméricas/genética , Neuronas/metabolismo , Neuropéptidos/genética , Transducción Genética/métodos , Animales , Anticuerpos Neutralizantes/farmacología , Factor Neurotrófico Derivado del Encéfalo/agonistas , Factor Neurotrófico Derivado del Encéfalo/antagonistas & inhibidores , Factor Neurotrófico Derivado del Encéfalo/genética , Región CA1 Hipocampal/citología , Región CA1 Hipocampal/efectos de los fármacos , Dependovirus/genética , Dependovirus/metabolismo , Expresión Génica , Vectores Genéticos/administración & dosificación , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina , Proteínas de Unión al GTP Monoméricas/metabolismo , Complejos Multiproteicos/agonistas , Complejos Multiproteicos/genética , Complejos Multiproteicos/metabolismo , Neuronas/citología , Neuronas/efectos de los fármacos , Neuropéptidos/metabolismo , Proteína Homóloga de Ras Enriquecida en el Cerebro , Ratas , Ratas Sprague-Dawley , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Trombina/antagonistas & inhibidores , Trombina/toxicidadRESUMEN
OBJECTIVES: The purpose of the present study was to investigate the diagnostic value of lactate for predicting bacteremia in female patients with acute pyelonephritis (APN). METHODS: We conducted a retrospective study of female patients with APN who visited the study hospital emergency department. The demographics, comorbidities, physiologies, and laboratory variables including white blood cell count and segmented neutrophil count, C-reactive protein, and initial serum lactate levels were collected and analyzed to identify associations with the presence of bacteremia. RESULTS: During the study period, a total of 314 patients were enrolled. One hundred twenty-three patients (39.2%) had bacteremia. Escherichia coli was the most frequent pathogen. Logistic regression analysis demonstrated that the lactate level was independently associated with the presence of bacteremia (odds ratio, 1.39 [95% confidence interval, 1.08-1.78]). The C-statistic of the lactate level was 0.67 (95% CI, 0.60-0.73). At a cutoff value of 1.4mmol/L, the lactate level predicted bacteremia with a sensitivity (53.7%), specificity (72.3%), positive predictive value (55.5%), negative predictive value (70.8%), positive likelihood ratio (1.93), and negative likelihood ratio (0.64). CONCLUSION: The initial serum lactate level showed poor discriminative performance for predicting bacteremia in female patients with APN.
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Bacteriemia/diagnóstico , Lactatos/sangre , Pielonefritis/complicaciones , Enfermedad Aguda , Anciano , Bacteriemia/sangre , Bacteriemia/etiología , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Valor Predictivo de las Pruebas , Pielonefritis/sangre , Pielonefritis/diagnóstico , Estudios RetrospectivosRESUMEN
Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on visceral afferent sensory neurons of the rat. Interestingly, PGE2 itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE2 potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin synthetase inhibitors by selectively targeting EP4 receptor/PKA pathway without interrupt prostaglandin synthesis.
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Dinoprostona/farmacología , Íleon/efectos de los fármacos , Ganglio Nudoso/efectos de los fármacos , Células Receptoras Sensoriales/metabolismo , Serotonina/metabolismo , Estómago/efectos de los fármacos , Aferentes Viscerales/metabolismo , Animales , Antiinflamatorios/farmacología , Carbazoles/farmacología , Relación Dosis-Respuesta a Droga , Enfermedades Gastrointestinales/tratamiento farmacológico , Íleon/inervación , Masculino , Neuronas Aferentes/metabolismo , Ondansetrón/farmacología , Técnicas de Placa-Clamp , Prostaglandinas/metabolismo , Pirroles/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Serotonina 5-HT3/metabolismo , Transducción de Señal , Estómago/inervación , Tiofenos/farmacología , Triazoles/farmacología , Xantonas/farmacologíaRESUMEN
Rosmarinic acid (α-o-caffeoyl-3,4-dihydroxyphenyllactic acid; RA) is a naturally occurring hydroxylated compound commonly found in species of the subfamily Nepetoideae of the Lamiaceae and Boraginaceae, such as Rosmarinus officinalis, Salvia officinalis, and Perilla frutescens. RA is biosynthesized from the amino acids L-phenylalanine and L-tyrosine by eight enzymes that include phenylalanine ammonia lyase and cinnamic acid 4-hydroxylase. RA can also be chemically produced by the esterification of caffeic acid and 3,4-dihydroxyphenyllactic acid. RA and its numerous derivatives containing one or two RA with other aromatic moieties are well known and include lithospermic acid, yunnaneic acid, salvianolic acid, and melitric acid. Recently, RA and its derivatives have attracted interest for their biological activities, which include anti-inflammatory, anti-oxidant, anti-angiogenic, anti-tumor, and anti-microbial functions. Clinically, RA attenuates T cell receptor-mediated signaling, attenuates allergic diseases like allergic rhinitis and asthma, and 2,4-dinitrofluorobenzene-induced atopic dermatitis-like symptoms, protects from neurotoxicity, and slows the development of Alzheimer's disease. These attributes have increased the demand for the biotechnological production and application of RA and its derivatives. The present review discusses the function and application of RA and its derivatives including the molecular mechanisms underlying clinical efficacy.
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Vías Biosintéticas , Biotecnología/métodos , Cinamatos/metabolismo , Depsidos/metabolismo , Factores Inmunológicos/metabolismo , Cinamatos/síntesis química , Depsidos/síntesis química , Factores Inmunológicos/química , Perilla frutescens/metabolismo , Rosmarinus/metabolismo , Salvia officinalis/metabolismo , Tecnología Farmacéutica/métodos , Ácido RosmarínicoRESUMEN
BACKGROUND: Adverse effects of emergency department (ED) crowding among critically ill patients are not well known. OBJECTIVES: We evaluated the association between ED crowding and inpatient mortality among critically ill patients admitted via the ED, and analyzed subsets of patients according to admission diagnosis. METHODS: We performed a post hoc analysis using data from a previous retrospective study. We enrolled admitted patients via the ED with an initial systolic blood pressure of 90 mm Hg or lower when presenting to the ED. The ED occupancy ratio was used as a measure of crowding. The primary outcome was inpatient mortality. Multivariable logistic regression models adjusted for potential confounding variables were constructed for the entire cohort and for subsets according to admission diagnosis (infection, cardiac and vascular disease, trauma, gastrointestinal bleeding, and other factors). RESULTS: A total of 1801 patients were enrolled, with a mortality rate of 14.6% (262 patients). The mortality rate by ED occupancy ratio quartile was 9.7% for the first quartile, 15.9% for the second quartile, 18.2% for the third quartile, and 14.4% for the fourth quartile. This resulted in adjusted odds ratios of 1.95, 2.51, and 1.93 and corresponding 95% confidence intervals of 1.23-3.12, 1.58-3.99, and 1.21-3.09 for the second, third, and fourth quartiles, respectively, compared with the first quartile. The effect of ED crowding was highest in the trauma subset, followed by the infection subset, whereas ED crowding did not appear to have any effect on the cardiac and vascular disease subsets. CONCLUSION: Emergency department crowding was associated with increased inpatient mortality among critically ill patients admitted via the ED.
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Enfermedad Crítica/mortalidad , Aglomeración , Servicio de Urgencia en Hospital , Hospitalización , Adulto , Anciano , Femenino , Tamaño de las Instituciones de Salud , Mortalidad Hospitalaria , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Retrospectivos , Tiempo de TratamientoRESUMEN
STUDY OBJECTIVE: The aim of the present study was to investigate the prognostic value of the initial serum lactate level in patients with community-acquired pneumonia (CAP). METHODS: We collected data on hospitalized adult patients with CAP via the study hospital emergency department between October 2012 and September 2013. Demographics, comorbidities, and physiologic and laboratory variables including initial C-reactive protein (CRP) and serum lactate level were extracted from the electronic medical record. The primary outcome was inpatient mortality. Comparisons between survivors and nonsurvivors were performed, and multivariable logistic regression analyses were constructed as dependent variables of both continuous and categorical varieties. RESULTS: A total of 397 patients were enrolled, and the mortality cases were 46 (11.6%). The mean lactate level was 1.7 ± 1.4 mmol/L and was significantly higher in the nonsurvivor group than in the survivor group (2.4 ± 2.2 mmol/L vs 1.6 ± 1.2 mmol/L). In the multivariable logistic regression model for inpatient mortality constructed using lactate, CRP, and laboratory variables of pneumonia severity index (PSI), lactate and CRP remained as significant factors, but laboratory variables of PSI were not. In other multivariable logistic regression models for the outcome constructed using collected laboratory variables and PSI, lactate remained as a significant factor (adjusted odds ratio, 1.24; 95% confidence interval, 1.01-1.53; P = .042 by continuous variable; adjusted odds ratio of third tertile, 2.60; 95% confidence interval, 1.02-6.66; P = .046 by category variable). C-reactive protein and albumin were also left as significant factors. CONCLUSIONS: The initial serum lactate level is independently associated with mortality in hospitalized patients with CAP. However, laboratory variables of PSI or others were not, except CRP and albumin.
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Infecciones Comunitarias Adquiridas/sangre , Infecciones Comunitarias Adquiridas/mortalidad , Mortalidad Hospitalaria , Ácido Láctico/sangre , Neumonía/sangre , Neumonía/mortalidad , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Comorbilidad , Femenino , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
The pathophysiology of cardiovascular diseases is complex and may involve oxidative stress-related pathways. Eriodictyol is a flavonoid present in citrus fruits that demonstrates anti-inflammatory, anti-cancer, neurotrophic, and antioxidant effects in a range of pathophysiological conditions including vascular diseases. Because oxidative stress plays a key role in the pathogenesis of cardiovascular disease, the present study was designed to verify whether eriodictyol has therapeutic potential. Upregulation of heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, in endothelial cells is considered to be helpful in cardiovascular disease. In this study, human umbilical vein endothelial cells (HUVECs) treated with eriodictyol showed the upregulation of HO-1 through extracellular-regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Further, eriodictyol treatment provided protection against hydrogen peroxide-provoked cell death. This protective effect was eliminated by treatment with a specific inhibitor of HO-1 and RNA interference-mediated knockdown of HO-1 expression. These data demonstrate that eriodictyol induces ERK/Nrf2/ARE-mediated HO-1 upregulation in human endothelial cells, which is directly associated with its vascular protection against oxidative stress-related endothelial injury, and propose that targeting the upregulation of HO-1 is a promising approach for therapeutic intervention in cardiovascular disease.
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Elementos de Respuesta Antioxidante , Antioxidantes/farmacología , Flavanonas/farmacología , Hemo-Oxigenasa 1/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Muerte Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hemo-Oxigenasa 1/genética , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Peróxido de Hidrógeno/toxicidad , Factor 2 Relacionado con NF-E2/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: To measure emergency department (ED) crowding, the emergency department occupancy ratio (EDOR) was introduced. OBJECTIVE: Our aim was to determine whether the EDOR is associated with mortality in adult patients who visited the study hospital ED. METHODS: We reviewed data on all patients who visited the ED of an urban tertiary academic hospital in Korea for 2 consecutive years. The EDOR is defined by the total number of patients in the ED divided by the number of licensed ED beds. We tested the association between the EDOR (quartile) and each outcome using a multivariable logistic regression analysis adjusted for potential confounders: age, sex, emergency medical services transport, transferred case, weekend visit, shift, triage acuity, visit cause of injury, operation, vital signs, intensive care unit or ward admission, and ED length of stay (quartile). The main outcome measures were survival status at discharge and at 1-7 days. RESULTS: A total of 54,410 adult patients were enrolled. The EDOR ranged from 0.41 to 2.31 and the median was 1.24. On multivariable analyses, in comparison with the lowest (first) quartile, the highest (fourth) quartile of the EDOR was associated with 1-day mortality (adjusted odds ratio [OR] = 1.42; 95% confidence interval [CI] 1.08-1.88), 2-day mortality (adjusted OR = 1.31; 95% CI 1.04-1.67), and 3-day mortality (adjusted OR = 1.27; 95% CI 1.02-1.58). The EDOR was not significantly associated with 4- to 7-day mortalities and overall mortality at discharge. CONCLUSIONS: The EDOR is associated with increased 1- to 3-day mortality even after controlling for potential confounders.
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Ocupación de Camas/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Mortalidad Hospitalaria , Adulto , Anciano , Aglomeración , Femenino , Hospitales de Enseñanza/estadística & datos numéricos , Hospitales Urbanos/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , República de Corea , Estudios RetrospectivosRESUMEN
Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.
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Flavonoid-rich ethanol extracts of licorice root have sedative and anxiolytic effects. Glabridin is a major flavonoid component from licorice which we evaluated by examining GABA responses in acutely isolated dorsal raphe neurons of the rat. Neurons were recorded with patch-clamp methods at a holding potential of - 50 mV. Glabridin potentiated GABA-induced responses by positively modulating GABAA receptor responses with different concentration range. GABA (2 × 10(-6) M)-evoked currents were potentiated in a stepwise pattern increasing glabridin concentration. Between 10(-12) and 10(-8) M glabridin increased GABA responses by about 140 % of the control. At concentrations above 10(-7) M, a much larger, dose-dependent potentiation occurred before reaching a plateau at 3 × 10-6 M glabridin. A hypnotic drug, zolpidem, also induced biphasic concentration-potentiation relationship. The glabridin potentiation ratio was 2.2 times larger than the maximum potentiation to the benzodiazepine receptor full agonist diazepam. Benzodiazepine receptor antagonist, flumazenil (3 × 10(-7) M), failed to inhibit glabridin (3 × 10(-7) M)-induced potentiation. This result implies that glabridin may exhibit sedative and hypnotic effects by potentiating GABAergic inhibition in dorsal raphe neurons by GABAA receptor actions.
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Encéfalo/efectos de los fármacos , GABAérgicos/farmacología , Glycyrrhiza/química , Hipnóticos y Sedantes/farmacología , Isoflavonas/farmacología , Fenoles/farmacología , Extractos Vegetales/farmacología , Receptores de GABA-A/metabolismo , Animales , Ansiolíticos/farmacología , Encéfalo/metabolismo , Diazepam/farmacología , Relación Dosis-Respuesta a Droga , Flumazenil/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Pentobarbital/farmacología , Raíces de Plantas , Piridinas/farmacología , Ratas , Ratas Sprague-Dawley , Zolpidem , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
OBJECTIVES: To examine whether the predictive value of the early warning score (EWS) could be improved by including rapid lactate levels, and to compare the modified EWS with the pre-existing risk scoring systems. DESIGN: Retrospective observational study in South Korea. SETTING: An urban, academic, tertiary hospital. PARTICIPANTS: Consecutive adult patients who were admitted to the medical intensive care unit via the emergency department (ED). OUTCOME MEASURES: A newly developed EWS--the VitalPAC EWS (ViEWS), was used in the present study. Lactate level, ViEWS and HOTEL score were obtained from patients at presentation to the ED, and APACHE II, SAPS II and SAPS III scores were obtained after admission. The area under curve of each risk scoring system for in-hospital, 1-week, 2-week and 4-week mortality was compared. RESULTS: 151 patients were enrolled and the mortality was 42.4%. The ViEWS-L score was calculated as follows: ViEWS-L score=ViEWS+lactate (mmol/l) according to the regression coefficient. The mean ViEWS-L score was 11.6±7.3. The ViEWS-L score had a better predictive value than the ViEWS score for hospital mortality (0.802 vs 0.742, p=0.009), 1-week mortality (0.842 vs 0.707, p<0.001), 2-week mortality (0.827 vs 0.729, p<0.001) and 4-week mortality (0.803 vs 0.732, p=0.003). The ViEWS-L score also had a better predictive value than the HOTEL and APACHE II scores. The predictive value of ViEWS-L was comparable with SAPS II and SAPS III. CONCLUSIONS: The ViEWS-L score performed as well as or better than the pre-existing risk scoring systems in predicting mortality in critically ill medical patients who were admitted to the medical intensive care unit via the ED.
Asunto(s)
Enfermedad Crítica/mortalidad , Lactatos/sangre , Índice de Severidad de la Enfermedad , Anciano , Biomarcadores/sangre , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Análisis de Regresión , República de Corea , Estudios RetrospectivosRESUMEN
In the first synapse of the blood-pressure-regulating pathway, a neurokinin (NK) family peptide substance P (SP) is release with an excitatory neurotransmitter, glutamate, to enhance the sensitivity of the baroreflex responses. However, the underlying mechanisms of action are not yet well understood. The effects of NK receptor antagonists and agonists on solitary tract stimulation-evoked excitatory postsynaptic responses were recorded using whole-cell patch-clamp recordings of neurons in the medial portion of the nucleus tractus solitarius (mNTS) in the brainstem. SP reduced the amplitude of the evoked excitatory postsynaptic currents (eEPSCs) and shifted the holding current inward, in a dose-dependent manner. The concentrations of SP needed to induce such responses were different between capsaicin-sensitive unmyelinated (C-type) and capsaicin-resistant myelinated (A-type) neurons. The perfusion of a NK1 receptor antagonist, sendide, reduced the amplitude of eEPSCs in all tested neurons but did not affect the levels of the holding current. A Neurokinin type 1 receptor (NK1 receptor) agonist, [Sar9, Met(O2)11]-SP, reduced the amplitude of the eEPSCs and shifted the holding current inward in capsaicin-resistant neurons; however, it failed to induce any significant changes in the capsaicin-sensitive neurons. Furthermore, a selective Neurokinin type 3 receptor (NK3 receptor) antagonist, SB223412, failed to induce any changes in any tested neuron. In current-clamp experiments, sendide reduced solitary tract (ST)-stimulation evoked firing of action potentials in both A- and C-type neurons. [Sar9, Met(O2)11]-SP suppressed the firing of the action potentials in C-type but not A-type neurons. In spontaneous synaptic recordings, SP reduced frequency of the sEPSCs in CAP sensitive neuron but NK1 agonist reduced at capsaicin resistant neurons. Taken together, the findings show that ST activation leads to the co-transmission of SP and glutamate and enhances baroreflex sensitivity by potentiating the amplitude of eEPSC in an NK1 receptor activity-dependent manner.