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Oxigenación por Membrana Extracorpórea , Humanos , Niño , Ácido Láctico , Factores de RiesgoRESUMEN
BACKGROUND: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. METHODS: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. RESULTS: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. CONCLUSIONS: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.
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COVID-19 , SARS-CoV-2 , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Anticuerpos ampliamente neutralizantes , COVID-19/prevención & control , Humanos , Ratones , SARS-CoV-2/genética , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
BACKGROUND: This study aims to compare lactate and central venous blood gas in the prediction of outcome in pediatric venoarterial mode extracorporeal membrane oxygenation (V-A ECMO). METHOD: This was a retrospective observational study conducted on patients undergoing V-A ECMO care in the pediatric intensive care unit of a tertiary medical center in Taiwan. Patients under 18 years of age undergoing V-A ECMO from January 2009 to April 2019 were included in this study. RESULTS: This study consisted of 47 children who received V-A ECMO with an overall weaning rate of 66.0%. The mean age was 5.5 years and mean ECMO duration was 11.6 days. Successful weaning group had significantly lower lactate levels at initial (58.7 ± 47.0 mg/dL vs. 108.0 ± 55.3 mg/dL, p = 0.003), 0-12 h (37.8 ± 29.0 mg/dL vs. 83.5 ± 60.0 mg/dL, p Z 0.001), and 12-24 h (29.4 ± 26.9 mg/dL vs. 69.1 ± 59.1 mg/dL, p = 0.003) after ECMO initiation; however, the central venous blood gas including pH, HCO3, CO2, base excess (BE), and O2 saturation showed no significant difference. The favorable outcome group had significantly lower lactate levels at 0-12 h (32.8 ± 26.3 mg/dL vs. 71.3 ± 53.3 mg/dL, p = 0.005), and 12-24 h (20.7 ± 10.2 mg/dL vs. 61.9 ± 53.5 mg/dL, p = 0.002); however, the HCO3 levels (26.2 ± 4.5 mmol/L vs. 22.9 ± 6.8 mmol/L, p = 0.042) and BE (2.2 ± 5.4 vs. 2.2 ± 8.5, p = 0.047) were significantly higher at 12-24 h. In multivariate logistic regression, 12-24 h lactate value was an independent factor for unfavorable outcomes (p = 0.015, odds ratio [OR] = 1.1) with the best cut-off value of 48.6 mg/dL (sensitivity 48%, specificity 100%). CONCLUSION: Lactate has better outcome prediction than central venous blood gas in pediatric V-A ECMO. The lactate value 12-24 h after ECMO initiation was an independent factor for unfavorable outcomes.
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Oxigenación por Membrana Extracorpórea , Adolescente , Dióxido de Carbono , Niño , Preescolar , Oxigenación por Membrana Extracorpórea/efectos adversos , Humanos , Unidades de Cuidado Intensivo Pediátrico , Ácido Láctico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Ductal dissection is rarely mentioned but intractable complication of ductal stenting. We demonstrate the dissection image under fluoroscopy and the use of a relatively large stent as an applicable treatment.
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Conducto Arterioso Permeable , Conducto Arterial , Atresia Pulmonar , Conducto Arterioso Permeable/complicaciones , Conducto Arterioso Permeable/cirugía , Cardiopatías Congénitas , Humanos , Atresia Pulmonar/complicaciones , Espasmo/complicaciones , StentsRESUMEN
BACKGROUND: Failure to thrive and poor weight gain are the main problems associated with ventricular septal defects complicated by heart failure in pediatric patients. Recent advances in transcatheter closure have enabled safe and effective interventions in these patients. OBJECTIVES: The purpose of this study was to describe our experience with transcatheter closure of ventricular septal defects in young children with low weight. METHODS: Pediatric patients weighing < 15 kg who underwent transcatheter closure of ventricular septal defects between January 2018 and December 2019 at our hospital were retrospectively enrolled. RESULTS: Twelve patients were enrolled: one with a muscular defect, two with outlet defects, and nine with perimembranous defects. Their median age was 24 (7-60) months, and their median weight before the procedure was 11.8 kg (4.7-14.9 kg; mean Z-score: -1.3). The median precordial echocardiographic defect diameter was 5.6 (2.0-9.3) mm. Successful transcatheter closure was achieved in 11 cases. The mean weight at 1-month follow-up after defect closure was 13.5 kg (6.2-19.8 kg; mean Z-score: -0.2). The mean length of hospitalization was 2.7 days. CONCLUSIONS: This study highlights the potential safety and therapeutic efficacy of transcatheter ventricular septal defect closure in infants with low weight. Considerable weight gain and heart failure symptom attenuation at 1 month after transcatheter closure were observed.
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PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease associated with rapid clinical deterioration and the need for intensive care; therefore, it is essential to identify clinical parameters related to mortality and establish prognostic factors correlated with unfavorable outcome in high risk patients whose treatment may fail. METHODS: Between January 2004 and December 2018, a total of 51 pediatric patients (less than 18 years old) who fulfilled the diagnostic criteria of HLH-2004 with documented results of bone marrow investigations at Kaohsiung Chang Gung Memorial Hospital were enrolled. The treatment protocol was based on hemophagocytic lymphohistiocytosis-94 (HLH-94) and HLH-2004. We retrospectively reviewed electronic medical records (EMR) including clinical features, length of intensive care unit (ICU) stay, serological tests, microscopic reports of bone marrow examination, and ultrasound examination reports at diagnosis to identify prognostic factors. The patients were divided into four groups based on etiology; these included infection associated hemophagocytic syndrome (IAHS), macrophage activation syndrome (MAS), malignancy associated hemophagocytic lymphohistiocytosis (MA-HLH), and idiopathic hemophagocytic lymphohistiocytosis (IHLH) to identify differences among the groups. RESULTS: Out of 51 patients enrolled, 27 patients had IAHS, 12 MAS, 8 MA-HLH, and 4 IHLH. The median age at diagnosis was 7 years. The overall mortality rate was 15.7% (there was no mortality in the MA-HLH group); the mean length of ICU stay was 6 ± 20.8 days. Longer activated partial thromboplastin time (aPTT) (p = 0.007), lower sodium concentration (p = 0.0007), and higher creatinine (p = 0.032) and aspartate aminotransferase (AST) (p = 0.017) were significantly related to mortality. Multivariate Cox regression analysis demonstrated that aPTT (p = 0.045, HR = 1.03, 95% CI = 1.0-1.1) was an independent risk factor for mortality. The receiver operating characteristic (ROC) curve showed that aPTT longer than 44.35 s was the cutoff value predicting mortality, with a sensitivity and specificity of 72% and 66.7%, respectively. CONCLUSION: MA-HLH had the lowest mortality rate, as most children died from the underlying malignant disease and not from HLH. Impaired liver and renal functions were related to mortality. Prolonged aPTT > 44.35 s is a strong predictive factor for mortality.
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Linfohistiocitosis Hemofagocítica , Neoplasias , Adolescente , Niño , Humanos , Unidades de Cuidados Intensivos , Linfohistiocitosis Hemofagocítica/diagnóstico , Estudios RetrospectivosRESUMEN
People may suffer from an intruded fear memory when the attributable traumatic events no longer exist. This is of highly clinical relevance to trauma-induced mental disorders, such as posttraumatic stress disorder (PTSD). Mechanism underlying PTSD largely lies in the abnormal process of fear extinction and a functional imbalance within amygdala associated fear circuit areas. Previous evidence suggested central dopamine plays a key role in the regulation of the fear memory process, yet it remains unclear whether the intervention of dopamine modulators would be beneficial for the fear extinction abnormalities. The present study examined the performance of Pavlovian conditioned fear and the changes of dopamine profiles following a subchronic 14-day regimen of aripiprazole (a partial agonist of dopamine D2 receptors to normalize the condition caused by dopamine imbalance) in rats previously experienced a psychologically traumatic procedure of single prolonged stress (SPS). The results demonstrated that aripiprazole at 5.0 mg/kg reversed the SPS-impaired fear memory dysfunction and the SPS-reduced dopamine efflux in the amygdala. The present study suggests a therapeutic potential of subchronic treatment with aripiprazole in managing patients suffered from fear extinction problem.
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Aripiprazol/farmacología , Miedo/efectos de los fármacos , Memoria/efectos de los fármacos , Trauma Psicológico/tratamiento farmacológico , Amígdala del Cerebelo/efectos de los fármacos , Animales , Aripiprazol/administración & dosificación , Condicionamiento Clásico/fisiología , Modelos Animales de Enfermedad , Extinción Psicológica/fisiología , Miedo/fisiología , Masculino , Ratas Sprague-Dawley , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/fisiopatología , Estrés Psicológico/tratamiento farmacológicoRESUMEN
RATIONALE: Neonatal gastric perforation is a rare and life-threatening disorder in neonates and is associated with high morbidity and mortality. However, the exact mechanisms of neonatal gastric perforation remain unknown. PATIENT CONCERNS: In this study, we reported 2 cases of neonatal gastric perforation and conducted a systematic review to analyze the prognostic factors for mortality. DIAGNOSES: Two neonates received a diagnosis of gastric perforation based on clinical presentation and imaging studies. The 2 patients underwent emergent surgery, which yielded favorable outcomes. INTERVENTIONS: We reviewed 168 cases from the literature as well as our 2 cases to analyze whether mortality in neonatal gastric perforation is associated with sex, gestational age, operation type, perforation location, or timing of perforation. OUTCOMES: The results revealed that mortality was significantly higher in preterm neonates (nâ=â80, Pâ<â.01) and the mortality group had a lower birth weight (nâ=â73, Pâ<â.05). The timing of perforation in the preterm subgroup was significantly earlier than that in the full-term subgroup (nâ=â90, Pâ<â.05). The outcomes about mortality of gastric perforation were significantly associated with preterm neonates (adjusted odds ratio: 4.21, 95% confidence interval: 1.28-13.88, Pâ<â.05). LESSONS: This study shows the prognostic factor of gastric perforation was significantly associated with preterm neonates. Furthermore, low-birth-weight full-term neonates had a relatively higher mortality rate than the normal-birth-weight full-term neonates. In addition, preterm neonates have an earlier timing of perforation.
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Gastropatías/diagnóstico , Peso al Nacer , Edad Gestacional , Humanos , Recién Nacido , Masculino , Gastropatías/cirugíaRESUMEN
This paper presents a wireless biosignal acquisition system-on-a-chip (WBSA-SoC) specialized for electrocardiogram (ECG) monitoring. The proposed system consists of three subsystems, namely, 1) the ECG acquisition node, 2) the protocol for standard IEEE 802.15.4 ZigBee system, and 3) the RF transmitter circuits. The ZigBee protocol is adopted for wireless communication to achieve high integration, applicability, and portability. A fully integrated CMOS RF front end containing a quadrature voltage-controlled oscillator and a 2.4-GHz low-IF (i.e., zero-IF) transmitter is employed to transmit ECG signals through wireless communication. The low-power WBSA-SoC is implemented by the TSMC 0.18-µm standard CMOS process. An ARM-based displayer with FPGA demodulation and an RF receiver with analog-to-digital mixed-mode circuits are constructed as verification platform to demonstrate the wireless ECG acquisition system. Measurement results on the human body show that the proposed SoC can effectively acquire ECG signals.
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Redes de Comunicación de Computadores/instrumentación , Redes de Comunicación de Computadores/normas , Electrocardiografía/instrumentación , Electrocardiografía/normas , Tecnología Inalámbrica/instrumentación , Tecnología Inalámbrica/normas , Diseño de Equipo , Análisis de Falla de Equipo , Guías como Asunto , Humanos , Internacionalidad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador/instrumentación , Relación Señal-RuidoRESUMEN
In this paper, we describe a graft polymerization/solvent immersion method for generating poly(2-hydroxyethyl methacrylate) (PHEMA) brushes in various patterns. We used a novel fabrication process, involving very-large-scale integration and oxygen plasma treatment, to generate well-defined patterns of polymerized PHEMA on patterned Si(100) surfaces. We observed brush- and mushroom-like regions for the PHEMA brushes, with various pattern resolutions, after immersing wafers presenting lines of these polymers in MeOH and n-hexane, respectively. The interaction between PHEMA and ferritin protein sheaths in MeOH and n-hexane (good and poor solvent for PHEMA, respectively) was used to capture and release ferritins from fluidic system. The "tentacles" behaver for PHEMA brushes was found through various solvents in fluidic system. Using high-resolution scanning electron microscopy, we observed patterned ferritin Fe cores on the Si surface after pyrolysis of the patterned PHEMA brushes and ferritin protein sheaths, which verify the "tentacles" behaver for PHEMA brushes.
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We used a novel fabricated process including electron beam and isotropic oxygen plasma to generate signal line patterns of polymerized 2-hydroxyethyl methacrylate (HEMA) on patterned Si(1 0 0) surfaces. Isotropic oxygen plasma was introduced to enhance the resolutions of the line and dots patterns of the PHEMA brush are approached to 350 nm and 2 µm, respectively. We established the surface grafting polymerization kinetics of the PHEMA chains on silicon surface by to fit the thickness and number-average molecular weight (M(n)). The propagation rate (k(p)) and active grafting specie deactivation rate (k(d)) lies in the range of ~3.6 × 10(-2) s(-1) M(-1) and 4.8 × 10(-5) s(-1), respectively. The measured thicknesses by ellipsometer and analyzed M(n) of "free" PHEMA by gel permeation chromatography (GPC) are fitted well by the polymerization kinetic model. In addition, aspect-ratios (height/width) are used to define the shape of patterned PHEMA brushes. The high-aspect-ratio of the PHEMA brush line with width of 350 nm is 0.27. We use a graft polymerization/solvent immersion method for generating various patterns of polymer brushes to investigate the deformation of the PHEMA brush through aspect-ratios.
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Polihidroxietil Metacrilato/química , Dióxido de Silicio/química , Electrones , Materiales Manufacturados , Estructura Molecular , Peso Molecular , Oxígeno , Polihidroxietil Metacrilato/metabolismo , Polimerizacion , Polímeros/química , Dióxido de Silicio/metabolismo , Solventes , Propiedades de SuperficieRESUMEN
Clinical evidence suggests that nicotine reduces anxiety in stressful situations. In the present study, we investigated the effect of nicotine on restraint-enhanced anxiety-like behavior, c-Fos expression, an index of neuronal activation in the brain, and plasma corticosterone. Two-hour restraint stress-enhanced anxiety-like behavior in the elevated plus-maze (EPM) and nicotine hydrogen tartrate (0.25 mg/kg, i.p.) attenuated the stress-induced changes. Pretreatment with the centrally acting nicotinic antagonist, mecamylamine (2 mg/kg), blocked nicotine's effects. In addition, restraint led to significant increases of c-Fos expression in several brain regions related to stress or anxiety including paraventricular hypothalamic nucleus (PVN), lateral hypothalamic area (LH), central amygdaloid nucleus (CeA), medial amygdaloid nucleus (MeA) and cingulate and retrosplenial cortices (Cg/RS), paraventricular thalamic nucleus (PVT), and basolateral amygdaloid nucleus (BLA). Nicotine attenuated the restraint-induced expression of c-Fos in the PVN, LH, CeA, MeA, and Cg/RS, while leaving the BLA and PVT unaffected. In contrast, nicotine did not reverse the increased levels of plasma corticosterone induced by restraint. These findings suggest that nicotine may modify the stress-induced behavioral changes via regulating the neuronal activation in selected brain regions rather than affecting hypothalamo-pituitary-adrenocortical axis hormone responses.