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1.
Stem Cells Dev ; 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39001828

RESUMEN

Traumatic injury to the spinal cord can lead to significant, permanent disability. Mammalian spinal cords are not capable of regeneration; in contrast, adult zebrafish are capable of such regeneration, fully recovering motor function. Understanding the mechanisms underlying zebrafish neuroregeneration may provide useful information regarding endogenous regenerative potential and aid in the development of therapeutic strategies in humans. DTXs regulate a variety of cellular processes. However, their role in neural regeneration has not been described. We found that zebrafish dtx2, encoding Deltex E3 ubiquitin ligase 2, is expressed in ependymo-radial glial cells in the adult spinal cord. After spinal cord injury, the heterozygous dtx2 mutant fish motor function recovered quicker than that of the wild-type controls. The mutant fish displayed increased ependymo-radial glial cell proliferation and augmented motor neuron formation. Moreover, her gene expression, downstream of Notch signaling, increased in Dtx2 mutants. Notch signaling inactivation by dominant-negative Rbpj abolished the increased ependymo-radial glia proliferation caused by Dtx2 deficiency. These results indicate that ependymo-radial glial proliferation is induced by Dtx2 deficiency, by activating Notch-Rbpj signaling to improve spinal cord regeneration and motor function recovery.

2.
J Clin Hypertens (Greenwich) ; 26(2): 187-196, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38214193

RESUMEN

There are limited data available regarding the connection between hypertension and heavy metal exposure. The authors intend to establish an interpretable machine learning (ML) model with high efficiency and robustness that identifies hypertension based on heavy metal exposure. Our datasets were obtained from the US National Health and Nutrition Examination Survey (NHANES, 2013-2020.3). The authors developed 5 ML models for hypertension identification by heavy metal exposure, and tested them by 10 discrimination characteristics. Further, the authors chose the optimally performing model after parameter adjustment by Genetic Algorithm (GA) for identification. Finally, in order to visualize the model's ability to make decisions, the authors used SHapley Additive exPlanation (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) algorithm to illustrate the features. The study included 19 368 participants in total. A best-performing eXtreme Gradient Boosting (XGB) with GA for hypertension identification by 16 heavy metals was selected (AUC: 0.774; 95% CI: 0.772-0.776; accuracy: 87.7%). According to SHAP values, Barium (0.02), Cadmium (0.017), Lead (0.017), Antimony (0.008), Tin (0.007), Manganese (0.006), Thallium (0.004), Tungsten (0.004) in urine, and Lead (0.048), Mercury (0.035), Selenium (0.05), Manganese (0.007) in blood positively influenced the model, while Cadmium (-0.001) in urine negatively influenced the model. Study participants' hypertension associated with heavy metal exposure was identified by an efficient, robust, and interpretable GA-XGB model with SHAP and LIME. Barium, Cadmium, Lead, Antimony, Tin, Manganese, Thallium, Tungsten in urine, and Lead, Mercury, Selenium, Manganese in blood are positively correlated with hypertension, while Cadmium in blood is negatively correlated with hypertension.


Asunto(s)
Compuestos de Calcio , Hipertensión , Mercurio , Metales Pesados , Óxidos , Selenio , Humanos , Cadmio/orina , Encuestas Nutricionales , Antimonio/orina , Manganeso , Talio/orina , Tungsteno/orina , Bario/orina , Estaño , Hipertensión/diagnóstico , Hipertensión/epidemiología , Metales Pesados/efectos adversos , Metales Pesados/orina , Aprendizaje Automático
3.
Chem Commun (Camb) ; 59(72): 10817-10820, 2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37602683

RESUMEN

A metal-free method for the dual activation of aryl phosphinate has been developed; the P-H and P-O bonds are sequentially activated by the Tf2O/DMSO system. Without the requirement of metals and unstable P-reagents, this one-pot procedure provides a convenient and practical access to a variety of aryl phosphonates. A mechanism involving twice generation of electrophilic P-species and two SN-processes is proposed on the basis of the control experiments.

4.
Technol Health Care ; 31(3): 1077-1091, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36617803

RESUMEN

BACKGROUND: To effectively monitor medical insurance funds in the era of big data, the study tries to construct an inpatient cost rationality judgement model by designing a virtuous cycle of inpatient cost supervision information system and exploring a complete set of inpatient cost supervision methods. OBJECTIVE: To lay the foundation for applying artificial intelligence (AI) technology in medical insurance cost control supervision and provide feasible paths and available tools for medical insurance cost control managers. METHODS: By way of collecting and cleaning electronic medical record (EMR) data from 2016 to 2018 of a city in East China, focusing on basic patient information and cost information, and using a combination of machine learning modeling and information system construction, the study tries to form a feasible inpatient cost supervision method and operation path. RESULTS: The set of the regulatory method, applied in nursing homes of a city in East China, is compelling. The accuracy rates of rationality judgement in different main diseases are stable up to 80%, the false positive rate is steady within 10%, and rehabilitation fee days of hospitalization, and the number of complications are important factors affecting the rationality of the inpatient cost. CONCLUSION: The model construction and optimization method combining machine learning and information system can make practical cost rationality judgement on medical institution's inpatient cost data, which can directly reflect the key influencing factors of relevant inpatient costs, and achieve the effect of guiding medical behavior and improving the efficiency of medical insurance fund use.


Asunto(s)
Inteligencia Artificial , Pacientes Internos , Seguro Médico General , Humanos , Macrodatos , Registros Electrónicos de Salud , Hospitalización , Aprendizaje Automático
5.
Shock ; 59(3): 368-374, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36562264

RESUMEN

ABSTRACT: Objectives: We attempted to identify and validate the subphenotypes of sepsis-associated liver dysfunction (SALD) using routine clinical information. Design: This article is a retrospective observational cohort study. Setting: We used the Medical Information Mart for Intensive Care IV database and the eICU Collaborative Research Database. Patients: We included adult patients (age ≥18 years) who developed SALD within the first 48 hours of intensive care unit (ICU) admission. We excluded patients who died or were discharged from the ICU within the first 48 hours of admission. Patients with abnormal liver function before ICU admission were also excluded. Measurements and Main Results: Patients in the MIMIC-IV 1.0 database served as a derivation cohort. Patients in the eICU database were used as validation cohort. We identified four subphenotypes of SALD (subphenotype α, ß, γ, δ) using K-means cluster analysis in 5234 patients in derivation cohort. The baseline characteristics and clinical outcomes were compared between the phenotypes using one-way analysis of variance/Kruskal-Wallis test and the χ 2 test. Moreover, we used line charts to illustrate the trend of liver function parameters over 14 days after ICU admission. Subphenotype α (n = 1,055) was the most severe cluster, characterized by shock with multiple organ dysfunction (MODS) group. Subphenotype ß (n = 1,179) had the highest median bilirubin level and the highest proportion of patients with underlying liver disease and coexisting coagulopathy (increased bilirubin group). Subphenotype γ (n = 1,661) was the cluster with the highest mean age and had the highest proportion of patients with chronic kidney disease (aged group). Subphenotype δ (n = 1,683) had the lowest 28-day and in-hospital mortality (mild group). The characteristics of clusters in the validation cohort were similar to those in the derivation cohort. In addition, we were surprised to find that GGT levels in subphenotype δ were significantly higher than in other subphenotypes, showing a different pattern from bilirubin. Conclusions: We identified four subphenotypes of SALD that presented with different clinical features and outcomes. These results can provide a valuable reference for understanding the clinical characteristics and associated outcomes to improve the management of patients with SALD in the ICU.


Asunto(s)
Hepatopatías , Sepsis , Humanos , Estudios Retrospectivos , Fenotipo , Análisis por Conglomerados , Unidades de Cuidados Intensivos
6.
Medicine (Baltimore) ; 101(45): e31763, 2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36397325

RESUMEN

Large-scale vaccination against the spread and mutation of COVID-19 is being implemented in many countries. We aimed to assess the effectiveness of certain vaccines (87.35% inactivated), mainly Sinovac - CoronaVac and Sinopharm (Beijing) - BBIBP-CorV, during the Omicron BA.2 pandemic by cross-sectional study. The study was conducted in a cabin hospital of Shanghai, China. A total of 1194 Covid-19 patients infected with Omicron BA.2 were enrolled and epidemiological survey information was collected from the subjects through electronic medical records and questionnaires, from March 23th to April 1st in 2022. Vaccine effectiveness was reflected by the occurrence of multi-dimensional symptoms while adjusting for confounding variables. In the unstandardized vaccinated group, the Covid-19 vaccine effectiveness of Omicron BA.2 in the male group was higher than in the female group (P = .0171). In the standardized vaccinated group, vaccine effectiveness in [20, 40) age group was higher than in other age groups (P = .0002). Adjusting for gender and age, Covid-19 vaccine effectiveness of Omicron BA.2 at the specific level was 87.42% (95% confidence interval [CI], 72.35-94.28, P < .0001), and 62.65% (95% CI, 1.47-85.84, P = .047) in the unstandardized vaccinated and the standardized vaccinated group, respectively. Covid-19 vaccine effectiveness of Omicron BA.2 was not apparent at the general level but remained effective for the specific symptom. Further development for the Covid-19 vaccine is necessary.


Asunto(s)
COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Humanos , Masculino , Femenino , Vacunas contra la COVID-19/uso terapéutico , Estudios Transversales , Gripe Humana/epidemiología , Pandemias , COVID-19/epidemiología , COVID-19/prevención & control , Eficacia de las Vacunas , China/epidemiología
7.
Comput Intell Neurosci ; 2022: 7352160, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35990118

RESUMEN

In recent years, studies have been conducted to quantify the relationship between microeconomic and macroeconomic development. Macroeconomics is the orientation of microeconomic development. Existing research hopes to quantify the relationship between macroeconomics and micro-firms, rather than just focusing on economic indicators. And some empirical studies try to use the relationship between them to discuss its usefulness for micro-firm decision-making. This article focuses on applying and developing aggregate earnings in connecting microenterprise earnings and macroeconomic development. To achieve this goal, this research did a comprehensive bibliometric analysis on macro-accounting on the two most influential databases, namely, Web of Science and Scopus. It used the information visualization software VOSviewer to draw knowledge maps to sort research lines. We also analyzed the research hotspots of macro-accounting in recent years according to the year scale and combined it with the neural network PSO-LSTM model to predict their future development. It turns out that the research on aggregate earnings related to economic growth has become a research hotspot in recent years. Scopus research and development potential is better than Web of Science in this field.


Asunto(s)
Bibliometría , Desarrollo Económico , Bases de Datos Factuales , Conocimiento , Programas Informáticos
8.
Foods ; 11(10)2022 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-35626995

RESUMEN

Polyphenols, the most abundant components in tea, determine the quality and health function of tea. The analysis of polyphenols in tea is a topic of increasing interest. However, the complexity of the tea matrix, the wide variety of teas, and the difference in determination purposes puts forward higher requirements for the detection of tea polyphenols. Many efforts have been made to provide a highly sensitive and selective analytical method for the determination and characterization of tea polyphenols. In order to provide new insight for the further development of polyphenols in tea, in the present review we summarize the recent literature for the detection of tea polyphenols from the perspectives of determining total polyphenols and individual polyphenols in tea. There are a variety of methods for the analysis of total tea polyphenols, which range from the traditional titration method, to the widely used spectrophotometry based on the color reaction of Folin-Ciocalteu, and then to the current electrochemical sensor for rapid on-site detection. Additionally, the application of improved liquid chromatography (LC) and high-resolution mass spectrometry (HRMS) were emphasized for the simultaneous determination of multiple polyphenols and the identification of novel polyphenols. Finally, a brief outline of future development trends are discussed.

9.
Br J Pharmacol ; 179(12): 2969-2985, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34997582

RESUMEN

BACKGROUND AND PURPOSE: As the only ionotropic receptor in the 5-HT receptor family, the 5-HT3 receptor (5-HT3 R) is involved in psychiatric disorders and its modulators have potential therapeutic effects for cognitive impairment in these disorders. However, it remains unclear how 5-HT3 Rs shape synaptic plasticity for memory function. EXPERIMENTAL APPROACH: Extracellular as well as whole-cell electrophysiological recordings were used to monitor hippocampal LTP and synaptic transmission in hippocampal slices in 5-HT3 AR knockout or 5-HT3 AR-GFP mice. Immunocytochemistry, qRT-PCR and western blotting were used to measure receptor expression. We also assessed hippocampal dependent cognition and memory, using the Morris water maze (MWM) and novel object recognition. KEY RESULTS: We found that 5-HT3 R dysfunction impaired hippocampal LTP in Schaffer collateral (SC)-CA1 pathway in hippocampal slices, by facilitating GABAergic inputs in pyramidal cells. This effect was dependent on 5-HT3 Rs on axon terminals. It resulted from reduced expression and function of the cannabinoid receptor 1 (CB1 R) co-localized with 5-HT3 Rs on axon terminals, and then led to diminishment of tonic inhibition of GABA release by CB1 Rs. Inhibition of CB1 Rs mimicked the facilitation of GABAergic transmission by 5-HT3 R disruption. Consequently, mice with hippocampal 5-HT3 R disruption exhibited impaired spatial memory in MWM tasks. CONCLUSION AND IMPLICATIONS: These results suggest that 5-HT3 Rs are crucial in enabling hippocampal synaptic plasticity via a novel CB1 R-GABAA -dependent pathway to regulate spatial memory.


Asunto(s)
Potenciación a Largo Plazo , Memoria Espacial , Animales , Región CA1 Hipocampal/metabolismo , Hipocampo/metabolismo , Humanos , Potenciación a Largo Plazo/fisiología , Trastornos de la Memoria/metabolismo , Ratones , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB1/metabolismo , Receptores de GABA-A/metabolismo , Serotonina/metabolismo , Ácido gamma-Aminobutírico/metabolismo
10.
J Formos Med Assoc ; 121(1 Pt 2): 314-318, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33994236

RESUMEN

BACKGROUND: Telemedicine helps to provide the safe management of stroke patients in the emergency department (ED) and has been used worldwide. However, we had limited experience of telestroke in Taiwan. We aimed to identify the quality of telestroke and compare it with the original face-to-face consultation model. METHODS: Among 178 consecutive acute ischemic stroke patients treated with intravenous tissue plasminogen activator (IVtPA) from January 1, 2018, to December 31, 2019, we compared two different consultation methods: face-to-face consultation and telestroke consultation. We collected data on demographics, the National Institutes of Health Stroke Scale (NIHSS) scores, Modified Rankin Scale (mRS) scores, time measurements (onset-to-arrival time, onset-to-telestroke activation time, and time of IVtPA administration (Door-to-Needle; DTN)). RESULTS: The mean age to receive a telestroke consultation was 66.6 years, 36% were female, and the median NIHSS score was 9. The median time from patient arrival to telestroke consult activation was 40 min, and the median DTN time was 11 min longer than for face-to-face consults (62 min versus 51 min, p = .01). Telestroke consultation, similar to a face-to-face consultation, resulted in safe IVtPA eligibility assessments and administration with post-thrombolysis ICH in 4% overall (4% telestroke, 3% face-to-face consultation; p = .851). The 90-day outcomes were not different for mRS score, dichotomized 0-2 (60% telestroke 59% face-to-face consultation; p = .961), or for mortality (16% telestroke, 9% face-to-face consultation; p = .292). CONCLUSION: In the ED, consultation via the telestroke program provides equal quality to the original face-to-face consultation model to manage ischemic stroke.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Telemedicina , Isquemia Encefálica/tratamiento farmacológico , Femenino , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Taiwán , Activador de Tejido Plasminógeno/uso terapéutico , Estados Unidos
11.
Int J Stroke ; 16(7): 784-791, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-32638639

RESUMEN

BACKGROUND AND PURPOSE: To examine sex differences in disease profiles and short-term outcomes after acute ischemic stroke treated with recombinant tissue plasminogen activator. METHODS: Eight national and regional stroke registries contributed individual participant data from mainland China, Japan, Philippines, Singapore, South Korea and Taiwan in 2005-2018. The primary outcome was ordinal-modified Rankin scale at 90 days. Key safety outcome was symptomatic intracerebral hemorrhage (sICH). RESULTS: Of 4453 patients included in the analyses, 1692 (36.3%) were women who were older, more likely to have a more severe neurological deficit, history of hypertension and atrial fibrillation, and a cardioembolic stroke compared to men. Women were more likely than men to have unfavorable shift of modified Rankin scale (fully adjusted odds ratio) (women vs. men) 1.14, 95% confidence interval 1.02-1.28). There was no significant sex difference for death 1.05 (0.84-1.31) or sICH (1.17, 0.89-1.54). Women were more likely to have unfavorable functional outcome with increasing age (P = 0.022 for interaction). In the age groups 70-80 and ≥80 years, women had a worse functional outcome compared to men (1.22, 1.02-1.47 and 1.43, and 1.06-1.92, respectively). CONCLUSION: In this pooled data from Asian acute stroke registries, women had poorer prognosis than men after receiving recombinant tissue plasminogen activator for acute ischemic stroke, which worsened with age. Women older than 70 appear to have a worse outcome than men which could be explained by greater stroke severity, more AF, and cardioembolic stroke.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Anciano de 80 o más Años , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/epidemiología , Asia Oriental , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Pronóstico , Sistema de Registros , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Terapia Trombolítica , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del Tratamiento
12.
Int J Stroke ; 14(7): 670-677, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31226919

RESUMEN

OBJECTIVE: To investigate the comparative efficacy and safety of the low-dose versus standard-dose alteplase using real-world acute stroke registry data from Asian countries. METHODS: Individual participant data were obtained from nine acute stroke registries from China, Japan, Philippines, Singapore, South Korea, and Taiwan between 2005 and 2018. Inverse probability of treatment weight was used to remove baseline imbalances between those receiving low-dose versus standard-dose alteplase. The primary outcome was death or disability defined by modified Rankin Scale scores of 2 to 6 at 90 days. Secondary outcomes were symptomatic intracerebral hemorrhage and death. Generalized linear mixed models with the individual registry as a random intercept were performed to determine associations of treatment with low-dose alteplase and outcomes. RESULTS: Of the 6250 patients (mean age 66 years, 36% women) included in these analyses, 1610 (24%) were treated with low-dose intravenous alteplase. Clinical outcomes for low-dose alteplase were not significantly different to those for standard-dose alteplase, adjusted odds ratios for death or disability: 1.00 (0.85-1.19) and symptomatic intracerebral hemorrhage 0.87 (0.63-1.19), except for lower death with borderline significance, 0.77 (0.59-1.01). CONCLUSIONS: The present analyses of real-world Asian acute stroke registry data suggest that low-dose intravenous alteplase has overall comparable efficacy for functional recovery and greater potential safety in terms of reduced mortality, to standard-dose alteplase for the treatment of acute ischemic stroke.


Asunto(s)
Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Asia , Pueblo Asiatico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros
13.
N Engl J Med ; 380(19): 1795-1803, 2019 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-31067369

RESUMEN

BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline. RESULTS: After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days. CONCLUSIONS: Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).


Asunto(s)
Isquemia Encefálica/diagnóstico por imagen , Fibrinolíticos/uso terapéutico , Imagen de Perfusión , Accidente Cerebrovascular/tratamiento farmacológico , Tiempo de Tratamiento , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Hemorragia Cerebral/inducido químicamente , Angiografía por Tomografía Computarizada , Femenino , Fibrinolíticos/efectos adversos , Humanos , Infusiones Intravenosas , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/prevención & control , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/mortalidad , Equipoise Terapéutico , Activador de Tejido Plasminógeno/efectos adversos
14.
J Stroke Cerebrovasc Dis ; 28(3): 815-820, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30573284

RESUMEN

BACKGROUND: Asians with atrial fibrillation carry a higher risk of ischemic stroke than non-Asians even under treatment of nonvitamin K antagonist oral anticoagulants. The purpose of the study was to observe the feasibility of intravenous thrombolytic therapy after administering a reversal agent, idarucizumab, in dabigatran-treated patients with acute ischemic stroke in Taiwan. METHODS: Dabigatran-treated patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (rt-PA) after idarucizumab reversal were enrolled in the retrospective nationwide study. The clinical data, treatment course, and outcomes were recorded. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) score. Any intracerebral hemorrhage (ICH) after rt-PA was detected by neuroimaging studies. RESULTS: Ten dabigatran-treated patients (6 men, mean age 71.10 ± 7.96 years) with acute ischemic stroke were included. Before stroke, the mean CHA2DS2-VASc score was 4.50 ± 1.57 and 8 patients (80%) received dabigatran 110 mg twice daily. All patients were treated with 5 g idarucizumab, following which the activated partial thromboplastin time normalized. Intravenous rt-PA (mean dose .78 mg/kg) was initiated a mean time of 11.11 minutes after idarucizumab infusion. The NIHSS score improved significantly after thrombolysis (16.0 ± 6.67 at admission to 9.38 ± 4.75 at discharge, P = .016). ICH developed in 3 patients (30%). Two of them were asymptomatic and 1 patient suffered from symptomatic ICH leading to mortality. CONCLUSION: Our data reconfirmed the feasibility of intravenous rt-PA for Asian stroke patients after reversal of dabigatran effect with idarucizumab.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Antitrombinas , Fibrilación Atrial/tratamiento farmacológico , Coagulación Sanguínea/efectos de los fármacos , Dabigatrán/antagonistas & inhibidores , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Antitrombinas/administración & dosificación , Antitrombinas/efectos adversos , Fibrilación Atrial/sangre , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Hemorragia Cerebral/inducido químicamente , Dabigatrán/administración & dosificación , Dabigatrán/efectos adversos , Esquema de Medicación , Estudios de Factibilidad , Femenino , Fibrinolíticos/efectos adversos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Taiwán/epidemiología , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/mortalidad , Factores de Tiempo , Activador de Tejido Plasminógeno/efectos adversos , Resultado del Tratamiento
15.
Front Behav Neurosci ; 12: 214, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30271334

RESUMEN

Spontaneous recognition tasks are widely used as a laboratory measure of memory in animals but give rise to high levels of behavioral noise leading to a lack of reliability. Previous work has shown that a modification of the procedure to allow continual trials testing (in which many trials are run concurrently in a single session) decreases behavioral noise and thus significantly reduces the numbers of rats required to retain statistical power. Here, we demonstrate for the first time that this improved method of testing extends to mice, increasing the overall power of the approach. Moreover, our results show that the new continual trials approach provides the additional benefits of heightened sensitivity and thus provides greater insight into the mechanisms at play. Standard (c57) and transgenic Alzheimer model (TASTPM) mice were tested both at 7 and 10 months of age in both object recognition (OR) and object-location (OL) spontaneous recognition tasks using the continual trials methodology. Both c57 and TASTPM mice showed age-dependent changes in performance in OR. While c57 mice also showed age-related changes in performance of OL, TASTPM mice were unable to perform OL at either age. Significantly, we demonstrate that differences in OL performance in c57s and TASTPM animals is a result of proactive interference rather than an absolute inability to recognize OL combinations. We argue that these continual trials approaches provide overall improved reliability and better interpretation of the memory ability of mice, as well as providing a significant reduction in overall animal use.

16.
J Am Heart Assoc ; 6(6)2017 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-28642220

RESUMEN

BACKGROUND: Pulse pressure (PP) is related to cardiac function, arterial stiffness, fluid status, and vascular events. This study aimed to explore the prognostic role of PP upon admission in patients with acute ischemic stroke (AIS) based on a nation-wide stroke registry. METHODS AND RESULTS: We evaluated the association between PP upon admission and outcomes 3 months after a stroke in patients who had an AIS registered in the Taiwan Stroke Registry, including 56 academic and community hospitals between 2006 and 2013. Three months after the stroke, unfavorable outcomes were defined using a modified Rankin scale of 3 to 6. Of 33 530 patients (female, 40.6%; mean age, 68.8±13.3 years) who had an AIS, PP upon admission had a reverse J-curve association with an unfavorable outcome. After adjusting for clinical variables, including AIS subtypes, initial National Institutes of Health Stroke Scale, and systolic and diastolic blood pressure upon admission, a PP of <50 mm Hg was associated with unfavorable outcomes (P<0.0001). Compared with patients with a PP of 50 to 69 mm Hg, the odds ratios for unfavorable outcomes were 1.24 (95% CI, 1.14-1.36) with a PP of 30 to 49 mm Hg and 1.85 (95% CI, 1.50-2.28) with a PP of <30 mm Hg. Moreover, the prognostic impact of PP upon admission was similar across all AIS subtypes. CONCLUSIONS: Low PP upon admission was associated with unfavorable patient outcomes in AIS.


Asunto(s)
Presión Sanguínea , Isquemia Encefálica/fisiopatología , Accidente Cerebrovascular/fisiopatología , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiología , Isquemia Encefálica/terapia , Distribución de Chi-Cuadrado , Evaluación de la Discapacidad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Admisión del Paciente , Pronóstico , Recuperación de la Función , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Taiwán/epidemiología , Factores de Tiempo
17.
BMC Infect Dis ; 17(1): 334, 2017 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-28486993

RESUMEN

BACKGROUND: Hospital-based case control studies have found family history of herpes zoster (HZ) was associated with risk of HZ, but the role of family history is not fully examined for other HZ-associated outcomes such as recurrent HZ, occurrence of postherpetic neuralgia (PHN), and HZ with different pain severities. METHODS: We conducted a population-based matched case control study. HZ cases that occurred during December 1, 2011 to November 30, 2012 were identified by face-to-face interview with all residents of eight selected communities/villages from three districts of Beijing, China. Medical records were reviewed for those who sought healthcare for HZ. For each case-patient, three, age-matched controls (±5 years) without HZ were enrolled from the same community/village of the matched case. Data on family history of HZ were collected by interview and only defined among first-degree relatives. RESULTS: A total of 227 case-patients and 678 matched controls were enrolled. Case-patients were more likely to report a family history of HZ [odds ratio (OR) =2.4, P = 0.002]. Compared with controls, association of family history decreased from HZ with PHN to HZ without PHN (OR = 6.0 and 2.3, respectively; P = 0.002 for trend), from recurrent HZ to primary HZ (OR = 9.4 and 2.2, respectively; P = 0.005 for trend), and from HZ with moderate or severe pain to HZ with mild or no pain (OR = 3.2 and 0.8, respectively; P < 0.001 for trend). CONCLUSIONS: Family history of HZ was associated with HZ occurrence and was more likely in HZ case-patients with PHN, recurrences, and painful HZ.


Asunto(s)
Herpes Zóster/etiología , Neuralgia Posherpética/etiología , Adolescente , Adulto , Anciano , Beijing/epidemiología , Estudios de Casos y Controles , Niño , Estudios Transversales , Familia , Femenino , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/epidemiología , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Neuralgia Posherpética/epidemiología , Recurrencia , Factores de Riesgo , Adulto Joven
18.
Artículo en Inglés | MEDLINE | ID: mdl-28367222

RESUMEN

Background. Patients suffering from stroke exhibit different levels of capability in retroflex tongues, in our clinical observation. This study aims to derive the association of tongue retroflexibility with the degree of severity for stroke patients. Methods. All ischemic stroke patients were collected from August 2010 to July 2013 in the Stroke Center, Changhua Christian Hospital, Taiwan. All participants underwent medical history collection and clinical examination, including tongue images captured by ATDS. Statistical analysis was performed to compare the differences of ischemic stroke patients with and without retroflex tongue. Result. Among the total of 308 cases collected, 123 patients cannot retroflex their tongues, that is, the non-RT group. The length of stay in the non-RT group, 32.0 ± 21.5, was longer than those of the RT counterparts, 25.9 ± 14.4 (p value: 0.007). The NIHSS on admission, 14.1 ± 7.8 versus 8.9 ± 5.2, was higher and the Barthel Index upon admission, 18.6 ± 20.7 and 35.0 ± 24.2, was lower for the non-RT patients than that of the RT counterparts. Also, the non-RT patients account for 60.2% and 75.6% for Barthel Index ≤ 17 and NIHSS ≥ 9, respectively. Conclusion. The stroke patients in non-RT group showed significantly poor prognosis and were more serious in the degree of severity and level of autonomy than RT group, indicating that the ability to maneuver tongue retroflex can serve as a simple, reliable, and noninvasive means for the prognosis of ischemic stroke patients.

19.
PLoS One ; 12(4): e0175434, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28388675

RESUMEN

BACKGROUND: Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR). METHODS: Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (<50%) in the extracranial internal carotid artery (ICA) and MCA, respectively. Logistic regression analysis, Kaplan-Meier method and Cox proportional hazard model were applied to assess relevant variables between groups. RESULTS: Of 6003 patients, 23.3% had MCA stenosis, 10.1% ICA stenosis, and 3.9% both MCA and ICA stenosis. Patients with MCA stenosis had greater initial NIHSS, higher likelihood of stroke-in-evolution, and more severe disability than those without (all p<0.001). Patients with MCA stenosis had higher prevalence of hypertension, diabetes and hypercholesterolemia. Patients with combined MCA and extracranial ICA stenosis had even higher NIHSS, worse functional outcome, higher risk of stroke recurrence or death (hazard ratio, 2.204; 95% confidence intervals, 1.440-3.374; p<0.001) at 3 months after stroke than those without MCA stenosis. CONCLUSIONS: In conclusion, MCA stenosis was more prevalent than extracranial ICA stenosis in ischemic stroke patients in Taiwan. Patients with MCA stenosis, especially combined extracranial ICA stenosis, had more severe neurological deficit and worse outcome.


Asunto(s)
Constricción Patológica/patología , Arteria Cerebral Media/patología , Accidente Cerebrovascular/fisiopatología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/patología
20.
PLoS One ; 11(7): e0159192, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27467732

RESUMEN

NMDA receptors have been widely reported to be involved in the regulation of synaptic plasticity through effects on long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD have been implicated in learning and memory processes. Besides synaptic plasticity, it is known that the phenomenon of gamma oscillations is critical in cognitive functions. Synaptic plasticity has been widely studied, however it is still not clear, to what degree synaptic plasticity regulates the oscillations of neuronal networks. Two NMDA receptor antagonists, ketamine and memantine, have been shown to regulate LTP and LTD, to promote cognitive functions, and have even been reported to bring therapeutic effects in major depression and Alzheimer's disease respectively. These compounds allow us to investigate the putative interrelationship between network oscillations and synaptic plasticity and to learn more about the mechanisms of their therapeutic effects. In the present study, we have identified that ketamine and memantine could inhibit LTD, without impairing LTP in the CA1 region of mouse hippocampus, which may underlie the mechanism of these drugs' therapeutic effects. Our results suggest that NMDA-induced LTD caused a marked loss in the gamma power, and pretreatment with 10 µM ketamine prevented the oscillatory loss via its inhibitory effect on LTD. Our study provides a new understanding of the role of NMDA receptors on hippocampal plasticity and oscillations.


Asunto(s)
Hipocampo/efectos de los fármacos , Ketamina/farmacología , Depresión Sináptica a Largo Plazo/efectos de los fármacos , Animales , Hipocampo/fisiología , Masculino , Memantina/farmacología , Ratones , Ratones Endogámicos C57BL , Potenciales Sinápticos/efectos de los fármacos
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