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Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.
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The osseous vascular endothelium encompasses a vast intricate framework that regulates bone remodeling. Osteoporosis, an age-associated systemic bone disease, is characterized by the degeneration of the vascular architecture. Nevertheless, the precise mechanisms underpinning the metamorphosis of endothelial cells (ECs) with advancing age remain predominantly enigmatic. In this study, we conducted a systematic analysis of differentially expressed genes (DEGs) and the associated pathways in juvenile and mature femoral ECs, utilizing data sourced from the Gene Expression Omnibus (GEO) repositories (GSE148804) and employing bioinformatics tools. Through this approach, we successfully discerned six pivotal genes, namely Adamts1, Adamts2, Adamts4, Adamts14, Col5a1, and Col5a2. Subsequently, we constructed a miRNA-mRNA network based on miRNAs displaying differential expression between CD31hiEMCNhi and CD31lowEMCNlow ECs, utilizing online repositories for prediction. The expression of miR-466i-3p and miR-466i-5p in bone marrow ECs exhibited an inverse correlation with age. Our in vivo experiments additionally unveiled miR-466i-5p as a pivotal regulator in osseous ECs and a promising therapeutic target for age-related osteoporosis.
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Células Endoteliales , MicroARNs , Células Endoteliales/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Animales , Osteoporosis/genética , Perfilación de la Expresión Génica , ARN Mensajero/genética , RatonesRESUMEN
OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.
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Linfoma , Mutación , Humanos , Masculino , Femenino , Estudios Retrospectivos , Niño , China/epidemiología , Linfoma/inmunología , Linfoma/genética , Preescolar , Lactante , Adolescente , Relevancia ClínicaRESUMEN
Abstract The osseous vascular endothelium encompasses a vast intricate framework that regulates bone remodeling. Osteoporosis, an age-associated systemic bone disease, is characterized by the degeneration of the vascular architecture. Nevertheless, the precise mechanisms underpinning the metamorphosis of endothelial cells (ECs) with advancing age remain predominantly enigmatic. In this study, we conducted a systematic analysis of differentially expressed genes (DEGs) and the associated pathways in juvenile and mature femoral ECs, utilizing data sourced from the Gene Expression Omnibus (GEO) repositories (GSE148804) and employing bioinformatics tools. Through this approach, we successfully discerned six pivotal genes, namely Adamts1, Adamts2, Adamts4, Adamts14, Col5a1, and Col5a2. Subsequently, we constructed a miRNA-mRNA network based on miRNAs displaying differential expression between CD31hiEMCNhi and CD31lowEMCNlow ECs, utilizing online repositories for prediction. The expression of miR-466i-3p and miR-466i-5p in bone marrow ECs exhibited an inverse correlation with age. Our in vivo experiments additionally unveiled miR-466i-5p as a pivotal regulator in osseous ECs and a promising therapeutic target for age-related osteoporosis.
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Abstract Tongluo-Qutong rubber plaster (TQRP), a typical Chinese patent medicine that contains 13 different herbal remedies, is widely used in clinical practice for the treatment of cervical spondylosis and osteoarthritis. However, due to a lack of in vitro transdermal studies, the active ingredients of TQRP have not been fully elucidated. This presents a huge obstacle for quality evaluation, pharmacokinetic studies and clinical safety assessment of TQRP. In this work, a UPLC/UV/MS/MS method was established and validated to evaluate five analytes in TQRP. The validation demonstrated linearity (r > 0.99), specificity (no co-eluting peaks at the retention times of the analytes), and precision (RSD < 15%) within acceptable parameters. A skin permeation study was performed to determine the concentrations of drugs delivered to the dermis. The 24-hour cumulative permeation of ferulic acid, aleo-emodin, emodin and piperine were 303.68, 709.31, 671.06 and 25561.01 ng/cm2, respectively. According to the fitting data of the TQRP active components, skin permeation was mainly due to a combination of passive diffusion and drug release after matrix erosion
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Animales , Masculino , Femenino , Ratones , Goma/clasificación , Piel/metabolismo , Técnicas In Vitro/métodos , Dermis/lesiones , Sensibilidad y Especificidad , Difusión , Liberación de Fármacos , Pueblos del Este de AsiaRESUMEN
We enrolled 98 infants (gestational age <33 weeks) in a pilot randomized trial of antibiotics vs no antibiotics; 55 were randomized (lower maternal infectious risk; symptoms expected for gestation). Adverse events did not differ significantly between the randomization arms. This trial establishes a framework for a larger multicentered trial.
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Antibacterianos/uso terapéutico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus agalactiae , Factores de Edad , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Proyectos PilotoRESUMEN
Manganese (Mn) is an essential trace element, but an excess or accumulation can be toxic. Until now, few studies have examined the effects of maternal Mn level on the risk of spontaneous preterm birth (SPB). The aims of this study were to examine the association between maternal Mn level and the risk of SPB at the early stage of pregnancy, and investigate whether this association was modified by single nucleotide polymorphisms (SNPs) in genes of superoxide dismutase (SOD) and catalase (CAT). We conducted a nested case-control study in three maternal and child health care hospitals in Shanxi province, China, from December 2009 to December 2013. From an overall cohort of 4229 women, 528 were included in our study, including 147 cases of SPB and 381 controls. Maternal blood samples were collected during 4-22 gestational weeks. The maternal serum concentrations of Mn was measured using inductively coupled plasma-mass spectrometry. We found the maternal Mn concentration in the case group (median: 1.55 ng/mL) was significantly higher than that in the control group (median: 1.27 ng/mL). Compared to the lowest level, the SPB risk was significantly increased to 1.44 (95%CI: 0.60-3.43), 2.42 (95%CI: 1.06-5.55) and 2.46 (95%CI: 1.08-5.62) respectively for the second, third and fourth quartiles in first trimester, but not significant in second trimester or overall. When exposure to a high Mn level, women who with AA (6.36, 95%CI: 1.57-25.71) and AG (3.04, 95%CI: 1.59-5.80) of rs2758352, with CC (2.34, 95%CI: 1.31-4.18) of rs699473, and with GG (2.26, 95%CI: 1.22-4.16) of rs769214 were more likely to develop a SPB, but not among women with other genotypes. In conclusion, high maternal serum Mn level is associated with the increased SPB risk in first trimester, and the association is modified by maternal SNPs of SOD2, SOD3 and CAT.
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Nacimiento Prematuro , Estudios de Casos y Controles , Niño , China , Femenino , Humanos , Recién Nacido , Manganeso , Polimorfismo de Nucleótido Simple , EmbarazoRESUMEN
OBJECTIVE: ADAMTS4 is a member of the ADAMTS4 family, which secretes proteinases. The mechanism of tumor metastasis may be correlated to its promotion of angiogenesis. It was determined whether ADAMTS4 participates in colorectal cancer progression. METHODS: The expression in clinical samples and CRC cell lines was investigated. Using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and RT-PCR, the expression of ADAMTS4 was determined in colorectal tumors of different cancer stages and anatomic sites, and in three cell lines of different aggressiveness. RESULTS: The overexpression of ADAMTS4 was observed in tissue samples by IHC, and this was mainly located in the cytoplasm, as detected by FISH. The qRT-PCR and western blot analyses further supported the clinical sample findings. CONCLUSION: The present data support the notion that the overexpression of ADAMTS4 in CRC might be useful as a non-invasive biomarker for detecting CRC in patients.
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Proteína ADAMTS4/análisis , Neoplasias Colorrectales/patología , Anciano , Análisis de Varianza , Biomarcadores de Tumor , Western Blotting , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Pronóstico , ARN Mensajero/análisis , Valores de Referencia , Regulación hacia ArribaRESUMEN
SUMMARY OBJECTIVE ADAMTS4 is a member of the ADAMTS4 family, which secretes proteinases. The mechanism of tumor metastasis may be correlated to its promotion of angiogenesis. It was determined whether ADAMTS4 participates in colorectal cancer progression. Methods The expression in clinical samples and CRC cell lines was investigated. Using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and RT-PCR, the expression of ADAMTS4 was determined in colorectal tumors of different cancer stages and anatomic sites, and in three cell lines of different aggressiveness. Results The overexpression of ADAMTS4 was observed in tissue samples by IHC, and this was mainly located in the cytoplasm, as detected by FISH. The qRT-PCR and western blot analyses further supported the clinical sample findings. Conclusion The present data support the notion that the overexpression of ADAMTS4 in CRC might be useful as a non-invasive biomarker for detecting CRC in patients.
RESUMO OBJETIVO ADAMTS4 é um membro da família ADAMTS4, que secreta proteinases. O mecanismo da metástase do tumor pode ser correlacionado a sua promoção da angiogênese. Determinou-se se ADAMTS4 participa na progressão do câncer colorretal. Métodos A expressão em amostras clínicas e linhas de células CRC foi investigada. Usando a imuno-histoquímica (IHC), a hibridação fluorescente in situ (HFIS) e o RT-PCR, a expressão de ADAMTS4 foi determinada em tumores colorretais de diferentes estágios do câncer e locais anatômicos, e em três linhas de células de níveis de agressividade distintos. Resultados A superexpressão de ADAMTS4 foi observada em amostras de tecido por IHC, e esta foi localizada principalmente no citoplasma, como detectado pelo HFIS. O qRT-PCR e a análise de wester blot corroboraram os resultados clínicos da amostra. Conclusão Os dados atuais corroboram a noção de que a superexpressão de ADAMTS4 no CRC pode ser útil como um biomarcador não invasivo para a detecção de CRC em pacientes.
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Humanos , Masculino , Femenino , Anciano , Neoplasias Colorrectales/patología , Proteína ADAMTS4/análisis , Pronóstico , Valores de Referencia , ARN Mensajero/análisis , Inmunohistoquímica , Neoplasias Colorrectales/genética , Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Regulación hacia Arriba , Western Blotting , Análisis de Varianza , Hibridación Fluorescente in Situ , Progresión de la Enfermedad , Línea Celular Tumoral , Persona de Mediana EdadRESUMEN
OBJECTIVE: To determine the effect of gastric residual aspiration and evaluation on preterm very low birth weight infants' gastrointestinal function, intestinal inflammation, and gastrointestinal mucosal bleeding. STUDY DESIGN: This single-center, randomized trial compared omission of gastric residuals vs prefeed gastric residuals in 143 infants ≤32 weeks of gestation with a birthweight of ≤1250 g for 6 weeks after birth. Serum levels of gastrin and motilin were collected between 14 and 21 days of life. Stools were collected at 3 and 6 weeks of age and analyzed for calprotectin and S100A12 levels. All stools were tested for occult blood for 6 weeks. RESULTS: Means for gastrin (P = .999) and motilin (P = .694) were similar between groups and there were no statistically significant differences in adjusted means for transformed calprotectin (P = .580), and S100A12 (P = .212). Both calprotectin (P = .003) and S100A12 (P = .002) increased from week 3 to week 6. The mean percentage of stools positive for occult blood (P = .888) were similar between the groups. CONCLUSIONS: Gastrointestinal function, intestinal inflammation, and gastrointestinal mucosal bleeding were similar whether aspiration and evaluation of gastric residuals were eliminated or not, suggesting routinely evaluating gastric residuals before every feeding may be unnecessary. TRIAL REGISTRATION CLINICALTRIALS.GOV:: NCT01863043.
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Nutrición Enteral/métodos , Enterocolitis Necrotizante/diagnóstico , Contenido Digestivo/química , Hemorragia Gastrointestinal/diagnóstico , Recién Nacido de muy Bajo Peso , Enterocolitis Necrotizante/epidemiología , Femenino , Estudios de Seguimiento , Hemorragia Gastrointestinal/epidemiología , Humanos , Incidencia , Recién Nacido , Masculino , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Herein, we report the antioxidant activity of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in pure and mixed solutions at different ratios, as well as of six different Cannabis sativa extracts containing various proportions of CBD and THC by using spectrophotometric (reducing power assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), hypochlorous acid (HOCl) scavenging assays) and electrochemical methods (cyclic voltammetry and differential pulse voltammetry). The isolated cannabinoids, the different stoichiometric ratios of CBD and THC, and the natural extracts proved to have remarkable antioxidant properties in all the methods employed in this work. The antioxidant activity of CBD and THC was compared against that of the well-defined antioxidants such as ascorbic acid (AA), resveratrol (Resv) and (-)-epigallocatechin-3-gallate (EGCG). Clear evidence of the synergistic and antagonistic effects between CBD and THC regarding to their antioxidant activities was observed. Moreover, a good correlation was obtained between the optical and electrochemical methods, which proved that the reported experimental procedures can easily be adapted to determine the antioxidant activity of extracts from various Cannabis sativa species and related compounds.
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Cannabidiol/química , Cannabis/química , Dronabinol/química , Depuradores de Radicales Libres/química , Extractos Vegetales/química , Cannabidiol/análisis , Dronabinol/análisis , Técnicas Electroquímicas/métodos , Depuradores de Radicales Libres/análisis , Extractos Vegetales/análisisRESUMEN
The degree of population exposure to various organic pollutants (OPs), including polycyclic aromatic hydrocarbons, organochlorinated pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers, can be determined by measuring their concentrations in human serum. However, performing large-scale measurements with such a variety of compounds in serum is challenging in terms of efficiency and cost. We describe herein the development of a high-efficiency extraction and sample cleanup protocol for simultaneous and quantitative analyses of OPs using gas chromatography-mass spectrometry. OPs, together with crude lipid impurities, were extracted from human serum with a mixture of n-hexane and methyl tert-butyl ether. A disperse sorbent composed of primary secondary amine and C18 (PSA/C18) was used to roughly remove co-extracted impurities. A combined column of neutral silica gel and neutral alumina oxide (AlO/SiG) was then used for deep cleanup. For the removal of impurities, the overall performance of our protocol for the analysis of OPs in serum was comparable to that of traditional gel permeation chromatography (GPC) and dramatically better than that of PSA/C18, which is a frequently used QuEChERS (quick, easy, cheap, effective, rugged, safe) based method. While both the proposed protocol and GPC yielded recoveries of 80%-110% for four classes of OPs, our protocol consumed about 10 times less solvent, resulting in lower experimental expenses and a lower risk of contamination from residual OPs in the solvent and other supplies. In contrast to GPC, our protocol also permits efficient batch processing of serum samples, allowing for large sample sizes such as those encountered in epidemiological studies.
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Análisis Químico de la Sangre/métodos , Contaminantes Ambientales/sangre , Hidrocarburos/sangre , Análisis Químico de la Sangre/normas , Cromatografía en Gel , Costos y Análisis de Costo , Cromatografía de Gases y Espectrometría de Masas , Hexanos/química , Humanos , Hidrocarburos/clasificación , Lípidos/química , Lípidos/aislamiento & purificación , Éteres Metílicos/química , Factores de TiempoRESUMEN
OBJECTIVES: To explore the effects of maternal folic acid supplementation alone during pregnancy on the incidence of low birth weight (LBW) and small-for-gestational-age (SGA) infant status. STUDY DESIGN: Data were derived from a large population-based cohort study performed in China to evaluate the prevention of neural tube defects with folic acid supplementation. The sample comprised 200 589 singleton live births registered in 2 southern Chinese provinces by mothers for whom detailed information on folic acid use was available. Gestational age was calculated from the first day of the last menstrual period. LBW was defined as a birth weight <2500 g. Infants were considered SGA when the age-adjusted birth weight was below the 10th percentile as defined by a national survey performed in 1998. Logistic regression was used to estimate the effects of folic acid after adjusting for the principal potential confounders. RESULTS: The overall incidence of LBW and SGA status was 2.18% and 5.82%, respectively. The incidence of LBW and SGA status was 2.09% and 5.73% in women who took folic acid, and 2.27% and 5.90% in those who did not. The adjusted risk ratios associated with folic acid use were 0.85 (95% CI: 0.80-0.90) for LBW and 0.93 (95% CI: 0.89-0.96) for SGA status. Folic acid use during pregnancy appeared to be particularly important to prevent LBW and SGA status. CONCLUSIONS: A maternal daily intake of 400 µg folic acid alone significantly reduced the risks of infant LBW and SGA status.
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Ácido Fólico/uso terapéutico , Recién Nacido de Bajo Peso , Recién Nacido Pequeño para la Edad Gestacional , Defectos del Tubo Neural/prevención & control , Nacimiento Prematuro/epidemiología , China , Estudios de Cohortes , Suplementos Dietéticos , Femenino , Edad Gestacional , Humanos , Incidencia , Lactante , Recién Nacido , Madres , Embarazo , Nacimiento Prematuro/tratamiento farmacológico , Estudios ProspectivosRESUMEN
BACKGROUND: Though there is considerable evidence that sphingosine kinase 1(SPHK1) plays a key role in hepatocellular carcinoma(HCC) progression, the prognostic value of SPHK1 expression in HCC with portal vein tumor thrombus (PVTT) remains unclear. Aims. The purpose of this study was to investigate the relationship of SPHK1 expression with PVTT and HCC recurrence after hepatectomy. METHODS: After screening of gene expression profiling of tumor cell lines, real-time PCR and immunohistochemistry were used to investigate the SPHK1 expression in PVTT and HCC samples. The clinical data of 199 HCC patients with nonmain PVTT who underwent liver resection with curative intention were studied. RESULTS: We identified SPHK1 as the most over-expressed gene in PVTT via gene expression profiling of one human PVTT cell line (CSQT-2). SPHK1 expression was an independent factor affecting survival (hazard ratio [HR] 1.799, 95% confidence interval [CI] 1.337-2.368, P < 0.001) and tumor recurrence (HR 1.451, 95% CI 1.087-1.935, P = 0.011). Patients with SPHK1 over-expression had a poorer prognosis than those with SPHK1 under-expression (P < 0.001 and P = 0.011 for survival and tumor recurrence). CONCLUSIONS: SPHK1 might represent a novel and useful prognostic marker of HCC progression in patients with PVTT.
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Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/enzimología , Neoplasias Hepáticas/enzimología , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Vena Porta , Trombosis de la Vena/enzimología , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Línea Celular Tumoral , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Hepatectomía , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Vena Porta/patología , Vena Porta/cirugía , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Transducción de Señal , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Trombosis de la Vena/etiología , Trombosis de la Vena/genética , Trombosis de la Vena/mortalidad , Trombosis de la Vena/cirugíaRESUMEN
OBJECTIVE: To describe the Single Photon Emission Microscope (SPEM), a state-of-the-art instrument for small animal SPECT imaging, and characterize its performance presenting typical images of different animal organs. METHODS: SPEM consists of two independent imaging devices based on high resolution scintillators, high sensitivity and resolution Electron-Multiplying CCDs and multi-pinhole collimators. During image acquisition, the mouse is placed in a rotational vertical holder between the imaging devices. Subsequently, an appropriate software tool based on the Maximum Likelihood algorithm iteratively produces the volumetric image. Radiopharmaceuticals for imaging kidneys, heart, thyroid and brain were used. The mice were injected with 74 to 148 MBq/0,3mL and scanned for 40 to 80 minutes, 30 to 60 minutes afterwards. During this procedure, the animals remained under ketamine/xilazine anesthesia. RESULTS: SPEM images of different mouse organs are presented, attesting the imaging capabilities of the instrument. CONCLUSION: SPEM is an innovative technology for small animal SPECT imaging providing high resolution images with appropriate sensitivity for pre-clinical research. Its use with appropriate radiotracers will allow translational investigation of several animal models of human diseases, their pharmacological treatment and the development of potential new therapeutic agents.
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Encéfalo/diagnóstico por imagen , Corazón/diagnóstico por imagen , Riñón/diagnóstico por imagen , Glándula Tiroides/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/instrumentación , Animales , Diseño de Equipo , Masculino , RatonesRESUMEN
Projections of countries' future populations, broken down by age and sex, are widely used for planning and research. They are mostly done deterministically, but there is a widespread need for probabilistic projections. We propose a bayesian method for probabilistic population projections for all countries. The total fertility rate and female and male life expectancies at birth are projected probabilistically using bayesian hierarchical models estimated via Markov chain Monte Carlo using United Nations population data for all countries. These are then converted to age-specific rates and combined with a cohort component projection model. This yields probabilistic projections of any population quantity of interest. The method is illustrated for five countries of different demographic stages, continents and sizes. The method is validated by an out of sample experiment in which data from 1950-1990 are used for estimation, and applied to predict 1990-2010. The method appears reasonably accurate and well calibrated for this period. The results suggest that the current United Nations high and low variants greatly underestimate uncertainty about the number of oldest old from about 2050 and that they underestimate uncertainty for high fertility countries and overstate uncertainty for countries that have completed the demographic transition and whose fertility has started to recover towards replacement level, mostly in Europe. The results also indicate that the potential support ratio (persons aged 20-64 per person aged 65+) will almost certainly decline dramatically in most countries over the coming decades.
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Tasa de Natalidad/tendencias , Censos , Demografía/métodos , Predicción/métodos , Naciones Unidas/estadística & datos numéricos , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Brasil/epidemiología , China/epidemiología , Femenino , Humanos , India/epidemiología , Esperanza de Vida/tendencias , Modelos Logísticos , Madagascar/epidemiología , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Distribución por Sexo , Adulto JovenRESUMEN
OBJECTIVES: To use high throughput techniques to analyze intestinal microbial ecology in premature neonates, who are highly susceptible to perturbations of the luminal environment associated with necrotizing enterocolitis (NEC) and late-onset sepsis. STUDY DESIGN: With non-culture-based techniques, we evaluated intestinal microbiota shortly after birth and during hospitalization in 23 neonates born at 23 to 32 weeks gestational age. Microbiota compositions were compared in 6 preterm infants in whom NEC, signs of systemic inflammation, or both developed with matched control subjects by using 16S ribosomal RNA pyrosequencing. RESULTS: Microbial DNA was detected in meconium, suggesting an intrauterine origin. Differences in diversity were detected in infants whose mothers intended to breast feed (P = .03), babies born to mothers with chorioamnionitis (P = .06), and in babies born at <30 weeks gestation (P = .03). A 16S ribosomal RNA sequence analysis detected Citrobacter-like sequences only in cases with NEC (3 of 4) and an increased frequency of Enterococcus-like sequences in cases and Klebsiella in control subjects (P = .06). The overall microbiota profiles in cases with NEC were not distinguishable from that in control subjects. CONCLUSIONS: Microbial DNA in meconium of premature infants suggests prenatal influences.