RESUMEN
The goal of this study was to identify potential transcriptomic markers in pediatric septic shock prognosis by an integrative analysis of multiple public microarray datasets. Using the R software and bioconductor packages, we performed a statistical analysis to identify differentially expressed (DE) genes in pediatric septic shock non-survivors, and further performed functional interpretation (enrichment analysis and co-expression network construction) and classification quality evaluation of the DE genes identified. Four microarray datasets (3 training datasets and 1 testing dataset, 252 pediatric patients with septic shock in total) were collected for the integrative analysis. A total of 32 DE genes (18 upregulated genes; 14 downregulated genes) were identified in pediatric septic shock non-survivors. Enrichment analysis revealed that those DE genes were strongly associated with acute inflammatory response to antigenic stimulus, response to yeast, and defense response to bacterium. A support vector machine classifier (non-survivors vs survivors) was also trained based on DE genes. In conclusion, the DE genes identified in this study are suggested as candidate transcriptomic markers for pediatric septic shock prognosis and provide novel insights into the progression of pediatric septic shock.
Asunto(s)
Choque Séptico , Transcriptoma , Biomarcadores , Niño , Biología Computacional , Perfilación de la Expresión Génica , Humanos , Análisis por Micromatrices , Choque Séptico/diagnóstico , Choque Séptico/genéticaRESUMEN
The goal of this study was to identify potential transcriptomic markers in pediatric septic shock prognosis by an integrative analysis of multiple public microarray datasets. Using the R software and bioconductor packages, we performed a statistical analysis to identify differentially expressed (DE) genes in pediatric septic shock non-survivors, and further performed functional interpretation (enrichment analysis and co-expression network construction) and classification quality evaluation of the DE genes identified. Four microarray datasets (3 training datasets and 1 testing dataset, 252 pediatric patients with septic shock in total) were collected for the integrative analysis. A total of 32 DE genes (18 upregulated genes; 14 downregulated genes) were identified in pediatric septic shock non-survivors. Enrichment analysis revealed that those DE genes were strongly associated with acute inflammatory response to antigenic stimulus, response to yeast, and defense response to bacterium. A support vector machine classifier (non-survivors vs survivors) was also trained based on DE genes. In conclusion, the DE genes identified in this study are suggested as candidate transcriptomic markers for pediatric septic shock prognosis and provide novel insights into the progression of pediatric septic shock.
Asunto(s)
Humanos , Niño , Choque Séptico/diagnóstico , Choque Séptico/genética , Transcriptoma , Biomarcadores , Biología Computacional , Perfilación de la Expresión Génica , Análisis por MicromatricesRESUMEN
The current study was designed to investigate the perinatal risk factors for low 1-min Apgar scores in term neonates. We retrospectively analyzed the maternal and neonatal clinical data of 10,550 infants who were born through vaginal delivery from 37 weeks 0 days to 41 weeks 6 days of single gestation from January 2013 to July 2018. Because the 1-min Apgar score reflects neonatal status at birth, we analyzed the risk factors for low (score <7) 1-min Apgar scores through logistic regression. Among these 10,550 neonates, 339 (3.2%) had low (score <7) 1-min Apgar scores. Among them, 321 (94.7%) were admitted to the neonatology department for further observation or treatment. Multivariate analysis revealed that educational background, body mass index, gestational age, pathological obstetrics, longer duration of the second stage of labor, forceps delivery or vacuum extraction, neonatal weight, neonatal sex, and meconium-stained amniotic fluid were independent risk factors for 1-min Apgar scores <7. Neonates who had low 1-min Apgar scores were more frequently admitted to the neonatology department for further observation or treatment. Early detection of risk factors and timely intervention to address these factors may improve neonatal outcomes at birth and reduce the rate of admission to the neonatology department.
Asunto(s)
Puntaje de Apgar , Parto Obstétrico , Adolescente , Adulto , Escolaridad , Femenino , Edad Gestacional , Humanos , Recién Nacido , Edad Materna , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
The current study was designed to investigate the perinatal risk factors for low 1-min Apgar scores in term neonates. We retrospectively analyzed the maternal and neonatal clinical data of 10,550 infants who were born through vaginal delivery from 37 weeks 0 days to 41 weeks 6 days of single gestation from January 2013 to July 2018. Because the 1-min Apgar score reflects neonatal status at birth, we analyzed the risk factors for low (score <7) 1-min Apgar scores through logistic regression. Among these 10,550 neonates, 339 (3.2%) had low (score <7) 1-min Apgar scores. Among them, 321 (94.7%) were admitted to the neonatology department for further observation or treatment. Multivariate analysis revealed that educational background, body mass index, gestational age, pathological obstetrics, longer duration of the second stage of labor, forceps delivery or vacuum extraction, neonatal weight, neonatal sex, and meconium-stained amniotic fluid were independent risk factors for 1-min Apgar scores <7. Neonates who had low 1-min Apgar scores were more frequently admitted to the neonatology department for further observation or treatment. Early detection of risk factors and timely intervention to address these factors may improve neonatal outcomes at birth and reduce the rate of admission to the neonatology department.
Asunto(s)
Humanos , Femenino , Recién Nacido , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Puntaje de Apgar , Parto Obstétrico , Estudios Retrospectivos , Factores de Riesgo , Edad Gestacional , Edad Materna , EscolaridadRESUMEN
OBJECTIVE: AZD6280 is a novel γ-aminobutyric acid A receptor modulator with higher in vitro efficacy at the α2,3 subtypes as compared to the α1 and α5 subtypes. This study compared the pharmacodynamic effects of single oral dose AZD6280 10 mg and 40 mg on the central nervous system with 2 mg of lorazepam. METHODS: Sixteen healthy males were enrolled into the double-blind, randomized, 4-way crossover study. Two validated central nervous system test batteries, Neurocart and CogState, were administered to measure drug effects on cognition, neurophysiologic function, and psychomotor and subjective feelings. Statistical analysis was performed using mixed model analysis of variance, with fixed factors of treatment, period, time and treatment by time, and random factors of subject, subject by treatment and subject by time, and the average prevalue as covariate. RESULTS: Most pharmacodynamic parameters were affected by lorazepam. AZD6280 induced dose-dependent smaller-than-lorazepam effects on saccadic peak velocity (SPV) (AZD6280, 10 mg vs. AZD6280, 40 mg vs. lorazepam [deg/s]: -22.6 vs. -50.0 vs. -62.9, P < 0.001), whereas the impacts on adaptive-tracking, body-sway, smooth-pursuit, and the one-card-learning tests were significant but much smaller than lorazepam. Thus, the slopes of regression lines for the ΔLog(Sway)-ΔSPV, ΔTracking-ΔSPV, and ΔSmooth-ΔSPV relations were flatter with AZD6280 than with lorazepam. AZD6280 caused a distinct electroencephalography signature from that of lorazepam. CONCLUSIONS: The SPV responses to AZD6280 suggest potential concentration-related anxiolytic effects, whereas the smaller SPV-normalized effects of AZD6280 on various non-SPV pharmacodynamic parameters suggest a more favorable side effect profile compared to lorazepam. Overall, the pharmacodynamic profile of AZD6280 matches the pharmacological specificity and selectivity of this compound at the α2,3 γ-aminobutyric acid A receptor subtypes.
Asunto(s)
Moduladores del GABA/farmacología , Voluntarios Sanos , Compuestos Heterocíclicos con 2 Anillos/farmacología , Receptores de GABA-A , Adolescente , Adulto , Estudios Cruzados , Método Doble Ciego , Moduladores del GABA/metabolismo , Compuestos Heterocíclicos con 2 Anillos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Receptores de GABA-A/metabolismo , Resultado del Tratamiento , Adulto JovenRESUMEN
Immune reconstitution inflammation syndrome typically occurs within days after patients undergo highly active anti-retroviral therapy and is a big hurdle for effective treatment of AIDS patients. In this study, we monitored immune reconstitution inflammation syndrome occurrence in 238 AIDS patients treated with highly active anti-retroviral therapy. Among them, immune reconstitution inflammation syndrome occurred in 47 cases (19.7%). Immune reconstitution inflammation syndrome patients had significantly higher rate of opportunistic infection (p < 0.001) and persistently lower CD4+ cell count (p < 0.001) compared to the non-immune reconstitution inflammation syndrome patients. In contrast, no significant differences in HIV RNA loads were observed between the immune reconstitution inflammation syndrome group and non-immune reconstitution inflammation syndrome group. These data suggest that a history of opportunistic infection and CD4+ cell counts at baseline may function as risk factors for immune reconstitution inflammation syndrome occurrence in AIDS patients as well as potential prognostic markers. These findings will improve the management of AIDS with highly active anti-retroviral therapy.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Terapia Antirretroviral Altamente Activa/efectos adversos , Síndrome Inflamatorio de Reconstitución Inmune/etiología , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Estudios Prospectivos , Factores de Riesgo , ARN Viral , Carga ViralRESUMEN
Immune reconstitution inflammation syndrome typically occurs within days after patients undergo highly active anti-retroviral therapy and is a big hurdle for effective treatment of AIDS patients. In this study, we monitored immune reconstitution inflammation syndrome occurrence in 238 AIDS patients treated with highly active anti-retroviral therapy. Among them, immune reconstitution inflammation syndrome occurred in 47 cases (19.7%). Immune reconstitution inflammation syndrome patients had significantly higher rate of opportunistic infection (p<0.001) and persistently lower CD4(+) cell count (p<0.001) compared to the non-immune reconstitution inflammation syndrome patients. In contrast, no significant differences in HIV RNA loads were observed between the immune reconstitution inflammation syndrome group and non-immune reconstitution inflammation syndrome group. These data suggest that a history of opportunistic infection and CD4(+) cell counts at baseline may function as risk factors for immune reconstitution inflammation syndrome occurrence in AIDS patients as well as potential prognostic markers. These findings will improve the management of AIDS with highly active anti-retroviral therapy.