Novel mutation in OTC gene causes neonatal death in twin brothers

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle. OTC locus is located in the short arm of X-chromosome. Authors report a case of a woman who gave birth to monozygotic male twins who later died because of severe neonatal-onset hyperammonaemic encephalopathy caused by a novel mutation of OTC gene. Post-mortem liver biopsy was taken from the second twin; afterwards, blood was drawn from the mother for examination. DNA sequence data showed that the mother was a carrier of the same novel mutation that was previously detected in the case of her son. In OTC deficiency, detection of female carriers is important for genetic counselling and eventual prenatal diagnosis.

Brain injury in experimental neonatal meningitis due to group B streptococci

We have characterized the pattern of brain injury in a rat model of meningitis caused by group B streptococci (GBS). Infant rats (12-14 days old; n = 69) were infected intracisternally with 10 microliters of GBS (log10(2.3) to 4.5 colony-forming units). Twenty hours later, illness was assessed clinically and cerebrospinal fluid was cultured. Animals were either immediately euthanized for brain histopathology or treated with antibiotics and examined later. Early GBS meningitis was characterized clinically by severe obtundation and seizures, and histopathologically by acute inflammation in the subarachnoid space and ventricles, a vasculopathy characterized by vascular engorgement, and neuronal injury that was most prominent in the cortex and often followed a vascular pattern. Incidence of seizures, vasculopathy and neuronal injury correlated with the inoculum size (p < 0.01). Early injury was almost completely prevented by treatment with dexamethasone. Within days after meningitis, injured areas became well demarcated and showed new cellular infiltrates. Thirty days post-infection, brain weights of infected animals treated with antibiotics were decreased compared to uninfected controls (1.39 +/- 0.18 vs 1.64 +/- 0.1 g; p < 0.05). Thus, GBS meningitis in this model caused extensive cortical neuronal injury resembling severe neonatal meningitis in humans.

JNK is activated but does not mediate hippocampal neuronal apoptosis in experimental neonatal pneumococcal meningitis

Pneumococcal meningitis is associated with caspase 3-dependent apoptosis of recently post-mitotic immature neurons in the dentate gyrus of the hippocampus. The death of these cells is implicated in the learning and memory deficits in patients surviving the disease. The stress-activated protein kinase c-Jun N-terminal kinase (JNK) has been shown to be an important mediator of caspase 3-dependent neuronal apoptosis. However, whether JNK is involved in hippocampal apoptosis caused by pneumococcal meningitis has so far not been investigated. Here we show in a neonatal rat model of pneumococcal meningitis that JNK3 but not JNK1 or JNK2 is activated in the hippocampus during the acute phase of infection. At the cellular level, JNK3 activation was accompanied in the dentate gyrus by markedly increased phosphorylation of its major downstream target c-Jun in early immature (Hu-positive) neurons, but not in migrating (doublecortin-positive) neurons, the cells that do undergo apoptosis. These findings suggested that JNK may not be involved in pneumococcal meningitis-induced hippocampal apoptosis. Indeed, although intracerebroventricular administration of D-JNKI-1 or AS601245 (two highly specific JNK inhibitors) inhibited c-Jun phosphorylation and protein expression in the hippocampus, hippocampal apoptosis was unaffected. Collectively, these results demonstrate that JNK does not mediate hippocampal apoptosis in pneumococcal meningitis, and that JNK may be involved in processes unrelated to apoptosis in this disease.

Neonatal steroids induce a down-regulation of tenascin-C and elastin and cause a deceleration of the first phase and an acceleration of the second phase of lung alveolarization

Pre- and postnatal corticosteroids are often used in perinatal medicine to improve pulmonary function in preterm infants. To mimic this clinical situation, newborn rats were treated systemically with dexamethasone (Dex), 0.1-0.01 mg/kg/day on days P1-P4. We hypothesized that postnatal Dex may have an impact on alveolarization by interfering with extracellular matrix proteins and cellular differentiation. Morphological alterations were observed on 3D images obtained by high-resolution synchrotron radiation X-ray tomographic microscopy. Alveolarization was quantified stereologically by estimating the formation of new septa between days P4 and P60. The parenchymal expression of tenascin-C (TNC), smooth muscle actin (SMA), and elastin was measured by immunofluorescence and gene expression for TNC by qRT-PCR. After Dex treatment, the first phase of alveolarization was significantly delayed between days P6 and P10, whereas the second phase was accelerated. Elastin and SMA expressions were delayed by Dex treatment, whereas TNC expression was delayed and prolonged. A short course of neonatal steroids impairs the first phase of alveolarization, most likely by altering the TNC and elastin expression. Due to an overshooting catch-up during the second phase of alveolarization, the differences disappear when the animals reach adulthood.

Comparison of IgG concentrations by radial immunodiffusion, electrophoretic gamma globulin concentrations and total globulins in neonatal foals

REASONS FOR PERFORMING STUDY: Failure of transfer of passive immunity (FTPI) in foals is associated with a risk of infection and death. The current diagnostic gold standard is quantification of immunoglobulins using radial immunodiffusion (IgG-RID). Routine diagnosis is often performed using semi-quantitative tests. Concentrations of serum electrophoretic gamma globulins (EGG) and total globulins may be useful to assess FTPI, but few studies have investigated their use. OBJECTIVES: To assess agreement between IgG-RID and EGG, and evaluate the accuracy of total globulin concentration to diagnose FTPI based on both IgG-RID and EGG. STUDY DESIGN: Prospective study. METHODS: 360 serum samples were harvested at 6-24 hours post natum from 60 German Warmblood foals. Concentrations of EGG, IgG-RID and total globulin concentration (calculated from total proteins and albumin) were measured. Agreement between EGG and IgG-RID was assessed using Bland-Altman plots and Passing-Bablok regression. The accuracy of total globulin concentration was assessed using rank correlation and ROC curve analysis. RESULTS: Good agreement was found with slightly lower EGG than IgG-RID concentrations (Bland-Altman systemic bias, -1.9 g/L) which was more pronounced at higher concentrations (regression equation: IgG-RID = -0.78 +1.28xEGG). Correlations between total globulin concentration and EGG, and total globulin concentration and IgG-RID were 0.93 and 0.79, respectively. The area under the curve was 0.982 and 0.952 for EGG <4 g/L and <8 g/L, and 0.953 and 0.899 for IgG-RID <4 g/L and <8 g/L. Sensitivities and specificities of total globulin concentration in the diagnosis of FTPI were comparable to commonly used screening tests, but cut-offs could be selected to achieve sensitivities of >95% with 71.2% (IgG-RID) and 90.5% (EGG) specificity for <4 g/L, and >90% with 66.0% (IgG-RID) and 87.9% (EGG) specificity for <8 g/L. CONCLUSIONS: There is good agreement between EGG and IgG-RID, with slightly more conservative estimates of immunoglobulins obtained using EGG. Total globulins may be a useful and economic quantitative screening test with cut-offs achieving high sensitivities, but analyser-specific cut-offs may be necessary. This article is protected by copyright. All rights reserved. KEYWORDS: IgG; electrophoresis; foal; globulins; horse; radial immunodiffusion. This article is protected by copyright. All rights reserved.

CXCR4/SDF1 interaction inhibits the primordial to primary follicle transition in the neonatal mouse ovary

The molecular mechanisms behind the entry of the primordial follicle into the growing follicle pool remain poorly understood. To investigate this process further, a microarray-based comparison was undertaken between 2-day postpartum mouse ovaries consisting of primordial follicles/naked oocytes only and those with both primordial follicles and newly activated follicles (7-day postpartum). Gene candidates identified included the chemoattractive cytokine stromal derived factor-1 (SDF1) and its receptor CXCR4. SDF1 and CXCR4 have been implicated in a variety of physiological processes including the migration of embryonic germ cells to the gonads. SDF1-alpha expression increased with the developmental stage of the follicle. Embryonic expression was found to be dichotomous post-genii cell migration, with low expression in the female. Immunohistochemical studies nonetheless indicate that the autocrine pattern of expression ligand and receptor begins during embryonic life. Addition of recombinant SDF1-alpha to neonatal mouse ovaries in vitro resulted in significantly higher follicle densities than for control ovaries. TUNEL analysis indicated no detectable difference in populations of apoptotic cells of treated or control ovaries. Treated ovaries also contained a significantly lower percentage of activated follicles as determined by measurement of oocyte diameter and morphological analysis. Treatment of cultured ovaries with an inhibitor of SDF1-alpha, AMD3100, ablated the effect of SDF1-alpha. By retaining follicles in an unactivated state, SDF1/CXCR4 signaling may play an important role in maintaining the size and longevity of the primordial follicle pool. (c) 2006 Elsevier Inc. All rights reserved.

Increasing nurse's knowledge of neonatal pain assessment through inservice education program

Recognizing neonatal pain is a challenge for nurses working with newborns due to the complexity of the pain phenomenon. Pain is subjective, and infants lack the ability to communicate, and their pain is difficult to recognize. The purpose of this study is to determine the effectiveness of education on the NICU nurses' ability to assess neonatal pain. With a better understanding of pain theory and the effects of pain on the newborn the nurse will be better able to assess newborns with pain. Designed as a quasi-experimental one-group pretest and posttest study, the data was collected on a convenience sample of 49 registered nurses employed in the neonatal and special care nursery units at a Childrens Hospital in the Miami area. The nurses were surveyed on the assessment of neonatal pain using the General Information and Pain Sensitivity Questionnaire. After the initial survey, the nurses were inserviced on neonatal pain assessment using a one hour inservice education program. One week after the intervention the nurse was asked to complete the questionnaire again. Data analysis involved comparision of pre and post intervention findings using descriptive methods, t test, correlation coefficients, and ANOVA , where applicable. Findings revealed a significant ( p=.006) increase in nurse's knowledge of neonatal pain assessment after completing the educational inservice when comparing the pre-test and post-test results.

Phenobarbital reduces EEG amplitude and propagation of neonatal seizures but does not alter performance of automated seizure detection

Objective: Phenobarbital increases electroclinical uncoupling and our preliminary observations suggest it may also affect electrographic seizure morphology. This may alter the performance of a novel seizure detection algorithm (SDA) developed by our group. The objectives of this study were to compare the morphology of seizures before and after phenobarbital administration in neonates and to determine the effect of any changes on automated seizure detection rates. Methods: The EEGs of 18 term neonates with seizures both pre- and post-phenobarbital (524 seizures) administration were studied. Ten features of seizures were manually quantified and summary measures for each neonate were statistically compared between pre- and post-phenobarbital seizures. SDA seizure detection rates were also compared. Results: Post-phenobarbital seizures showed significantly lower amplitude (p < 0.001) and involved fewer EEG channels at the peak of seizure (p < 0.05). No other features or SDA detection rates showed a statistical difference. Conclusion: These findings show that phenobarbital reduces both the amplitude and propagation of seizures which may help to explain electroclinical uncoupling of seizures. The seizure detection rate of the algorithm was unaffected by these changes. Significance: The results suggest that users should not need to adjust the SDA sensitivity threshold after phenobarbital administration.

Reducir la mortalidad infantil: Un objetivo del desarrollo sostenible y una oportunidad para la enfermería.

os Objetivos de Desarrollo Sostenible (ODS) guiarán las decisiones que adoptemos durante los próximos 15 años y en ellos se lograron avances en el marco de los Objetivos de Desarrollo del Milenio (ODM) cuyos objetivos con la salud materna, neonatal e infantil y con la salud reproductiva distan de haber sido alcanzados. La mortalidad infantil es importante porque es un indicador de la utilización, accesibilidad y disponibilidad del sistema de salud de los habitantes, especialmente de los niños. La tasa de mortalidad infantil ha reducido a la mitad en 25 años (1990 a 2015) más la meta mundial del ODM de una reducción de 2/3 no se alcanzó. En 2015 la mayoría de las muertes en niños menores de cinco años fueron causadas por enfermedades neonatales, infecciosas o de nutrición. Estas muertes se pueden prevenir y tratar fácilmente en casa o en los centros de salud. Las enfermeras y parteras están en la primera línea de la prestación de estos servicios. En muchos países son líderes o actores clave en los equipos de salud interdisciplinarios. Ofrecen una amplia gama de servicios de enfermería y partería en todos los niveles del sistema de salud. Las Naciones Unidas piden la equidad en salud a través de la cobertura de salud universal, de modo que todos los niños puedan acceder a los servicios de salud esenciales. Pero esto sólo se puede lograr con el apoyo de los recursos humanos de salud, y de enfermería en particular. La investigación ha demostrado que más de la mitad de los casi 11 millones de muertes de niños/año, podrían salvarse mediante medidas como vacunas, mejora de la atención de la familia y las prácticas de lactancia, promover la planificación familiar y la educación de las mujeres. Para la lograr; la calidad, cantidad y relevancia de la fuerza de trabajo de enfermería y obstetricia tendrán que ser asegurado. La práctica de enfermería, a través de su experiencia directa y intervenciones terapéuticas centradas en el cliente y capaz de proporcionar cuidados eficaces de acuerdo con los contextos de salud y enfermedad es fundamental. Para alcanzar los ODS se necesitan datos sobre los recursos humanos de salud. La investigación de enfermería es decisiva en la creación y explicación de datos que incluyen los números, competencias, lugares de práctica y calidad de los resultados en el plano local, nacional e internacional. También es necesario documentación sobre la función y el trabajo de las enfermeras en la creación, soporte y mantenimiento de los sistemas de salud. Por fin, las políticas relacionadas con los recursos humanos deben estar basadas en la evidencia, y las enfermeras no se pueden olvidar su papel clave en las mesas de política.

Prevalencia de artritis séptica neonatal en un hospital universitario

Introducción: La artritis séptica neonatal es un padecimiento poco común que se ha relacionado con recién nacidos internados en la unidad de cuidados intensivos neonatal, cuyo principal factor de riesgo es el uso previo de catéter central. Objetivo: establecer la prevalencia de la artritis séptica neonatal en nuestro Hospital. Material y método: estudio observacional descriptivo de prevalencia. Se incluyeron todos los recién nacidos con diagnostico de artritis séptica neonatal internados un la unidad de cuidados intermedios e intensivos neonatal del Hospital Universitario Dr. José Eleuterio González del año 2003 al 2007. Se revisaron los expedientes y se registraron variables generales, factores de riesgo, bacteriología y mortalidad. Resultados: Se diagnosticaron 26 casos de artritis séptica neonatal durante el periodo de tiempo estudiado, solo 20 casos lograron criterios de inclusión: la prevalencia fue de 1.2 casos por cada 1,000 nacidos. La edad gestacional fue 39.2 ± 1.3 semanas, con peso 3193 ± 709 g. El factor de riesgo que se presento con mas frecuencia fue el antecedente de uso previo de catéter en 75% de los casos. Se aisló microorganismo en 80% de los casos, los bacterias grampositivas se aislaron en 80% de los casos; el Staphylococcus aureus fue el microorganismo aislado predominantemente en 75% de los casos. La presentación poliarticular fue en 40% de los casos. La mortalidad fue de 0%. Conclusiones: La prevalencia fue menor a lo reportado en la literatura. Los microorganismos grampositivos continúan siendo los microorganismos predominantes en la artritis séptica neonatal. La mortalidad es baja.

Factores relacionados a sépsis neonatal. Unidad de Neonatología Clínica Humanitaria-Fundación Pablo Jaramillo

Se realizó un estudio observacional en recién nacidos sépticos ocurridos en la Unidad de Neonatología de la Fundación Humanitaria Pablo Jaramillo, durante el período de enero de 2009 a diciembre de 2011, con el objetivo de analizar la incidencia de antecedentes maternos y parámetros propios del recién nacido como posibles factores de riesgo para la sepsis, los parámetros de laboratorio que contribuyen a diagnosticar procesos infecciosos en el recién nacido y el desenlace que tuvieron los mismos. Durante este tiempo ingresaron 164 casos con riesgo de sepsis, sospecha de sepsis y sepsis bacteriana (42.62 /1000 nacidos vivos) y la mortalidad fue del 3.04%. Predominó la sepsis de inicio precoz sobre la tardía. Los principales antecedentes maternos fueron la ruptura prematura de membranas seguido de la infección de vías urinarias. En cuanto a los factores del recién nacido prevaleció el sexo masculino, prematurez y de bajo peso al nacer

Computer and laboratory simulation in the teaching of neonatal nursing: innovation and impact on learning

Objectives: to evaluate the cognitive learning of nursing students in neonatal clinical evaluation from a blended course with the use of computer and laboratory simulation; to compare the cognitive learning of students in a control and experimental group testing the laboratory simulation; and to assess the extracurricular blended course offered on the clinical assessment of preterm infants, according to the students. Method: a quasi-experimental study with 14 Portuguese students, containing pretest, midterm test and post-test. The technologies offered in the course were serious game e-Baby, instructional software of semiology and semiotechnique, and laboratory simulation. Data collection tools developed for this study were used for the course evaluation and characterization of the students. Nonparametric statistics were used: Mann-Whitney and Wilcoxon. Results: the use of validated digital technologies and laboratory simulation demonstrated a statistically significant difference (p = 0.001) in the learning of the participants. The course was evaluated as very satisfactory for them. The laboratory simulation alone did not represent a significant difference in the learning. Conclusions: the cognitive learning of participants increased significantly. The use of technology can be partly responsible for the course success, showing it to be an important teaching tool for innovation and motivation of learning in healthcare.

An Efficient Protocol For The Generation Of Monocyte Derived Dendritic Cells Using Serum-free Media For Clinical Applications In Post Remission Aml Patients.

Protocols for the generation of dendritic cells (DCs) using serum as a supplementation of culture media leads to reactions due to animal proteins and disease transmissions. Several types of serum-free media (SFM), based on good manufacture practices (GMP), have recently been used and seem to be a viable option. The aim of this study was to evaluate the results of the differentiation, maturation, and function of DCs from Acute Myeloid Leukemia patients (AML), generated in SFM and medium supplemented with autologous serum (AS). DCs were analyzed by phenotype characteristics, viability, and functionality. The results showed the possibility of generating viable DCs in all the conditions tested. In patients, the X-VIVO 15 medium was more efficient than the other media tested in the generation of DCs producing IL-12p70 (p=0.05). Moreover, the presence of AS led to a significant increase of IL-10 by DCs as compared with CellGro (p=0.05) and X-Vivo15 (p=0.05) media, both in patients and donors. We concluded that SFM was efficient in the production of DCs for immunotherapy in AML patients. However, the use of AS appears to interfere with the functional capacity of the generated DCs.

Temporomandibular Dysfunction Post-craniotomy: Evaluation Between Pre- And Post-operative Status.

To identify risk factors associated with post-operative temporomandibular joint dysfunction after craniotomy. The study sample included 24 patients, mean age of 37.3 ± 10 years; eligible for surgery for refractory epilepsy, evaluated according to RDC/TMD before and after surgery. The primary predictor was the time after the surgery. The primary outcome variable was maximal mouth opening. Other outcome variables were: disc displacement, bruxism, TMJ sound, TMJ pain, and pain associated to mandibular movements. Data analyses were performed using bivariate and multiple regression methods. The maximal mouth opening was significantly reduced after surgery in all patients (p = 0.03). In the multiple regression model, time of evaluation and pre-operative bruxism were significantly (p < .05) associated with an increased risk for TMD post-surgery. A significant correlation between surgery follow-up time and maximal opening mouth was found. Pre-operative bruxism was associated with increased risk for temporomandibular joint dysfunction after craniotomy.

Neonatal Outcomes Of Late Preterm And Early Term Birth.

To compare neonatal deaths and complications in infants born at 34-36 weeks and six days (late preterm: LPT) with those born at term (37-41 weeks and six days); to compare deaths of early term (37-38 weeks) versus late term (39-41 weeks and six days) infants; to search for any temporal trend in LPT rate. A retrospective cohort study of live births was conducted in the Campinas State University, Brazil, from January 2004 to December 2010. Multiple pregnancies, malformations and congenital diseases were excluded. Control for confounders was performed. The level of significance was set at p<0.05. After exclusions, there were 17,988 births (1653 late preterm and 16,345 term infants). A higher mortality in LPT versus term was observed, with an adjusted odds ratio (OR) of 5.29 (p<0.0001). Most complications were significantly associated with LPT births. There was a significant increase in LPT rate throughout the study period, but no significant trend in the rate of medically indicated deliveries. A higher mortality was observed in early term versus late term infants, with adjusted OR: 2.43 (p=0.038). LPT and early term infants have a significantly higher risk of death.