Impact of Congenital Heart Disease on Brain Development and Neurodevelopmental Outcome

Advances in cardiac surgical techniques and perioperative intensive care have led to improved survival in babies with congenital heart disease (CHD). While it is true that the majority of children with CHD today will survive, many will have impaired neurodevelopmental outcome across a wide spectrum of domains. While continuing to improve short-term morbidity and mortality is an important goal, recent and ongoing research has focused on defining the impact of CHD on brain development, minimizing postnatal brain injury, and improving long-term outcomes. This paper will review the impact that CHD has on the developing brain of the fetus and infant. Neurologic abnormalities detectable prior to surgery will be described. Potential etiologies of these findings will be discussed, including altered fetal intrauterine growth, cerebral blood flow and brain development, associated congenital brain abnormalities, and risk for postnatal brain injury. Finally, reported neurodevelopmental outcomes after surgical repair of CHD will be reviewed

Cerebral pressure passivity in newborns with encephalopathy undergoing therapeutic hypothermia

We extended our recent modification of the power spectral estimation approach to quantify spectral coherence. We tested both the standard and the modified approaches on simulated data, which showed that the modified approach was highly specific and sensitive to the coupling introduced in the simulation while the standard approach lacked these features. We also applied the modified and standard approaches to quantify the pressure passivity in 4 infants receiving therapeutic hypothermia. This was done by measuring the coupling between continuous cerebral hemoglobin differences and mean arterial blood pressure. Our results showed that the modified approach identified a lower pressure passivity index (PPI, percent time the coherence was above a predefined threshold) than the standard approach (P = 0.0027)

Coagulopathy in newborns with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia: A retrospective case-control study

Background Newborns with hypoxic ischemic encephalopathy (HIE) are at risk for coagulopathy due to systemic oxygen deprivation. Additionally, therapeutic hypothermia (TH) slows enzymatic activity of the coagulation cascade, leading to constitutive prolongation of routinely assessed coagulation studies. The level of laboratory abnormality that predicts bleeding is unclear, leading to varying transfusion therapy practices. Methods HIE infants treated with TH between 2008–2012 were included in this retrospective study. Initial, minimum (min) and maximum (max) values of International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen (Fib) and platelet (PLT) count (measured twice daily during TH) were collected. Bleeding was defined as clinically significant if associated with 1) decreased hemoglobin (Hb) by 2 g/dL in 24 hours, 2) transfusion of blood products for hemostasis, or 3) involvement of a critical organ system. Laboratory data between the bleeding group (BG) and non-bleeding group (NBG) were compared. Variables that differed significantly between groups were evaluated with Receiver Operating Characteristic Curve (ROC) analyses to determine cut-points to predict bleeding. Results Laboratory and bleeding data were collected from a total of 76 HIE infants with a mean (±SD) birthweight of 3.34 ± 0.67 kg and gestational age of 38.6 ± 1.9 wks. BG included 41 infants. Bleeding sites were intracranial (n = 13), gastrointestinal (n = 19), pulmonary (n = 18), hematuria (n = 11) or other (n = 1). There were no differences between BG and NBG in baseline characteristics (p \u3e 0.05). Both groups demonstrated INR and aPTT values beyond the acceptable reference ranges utilized for full tem newborns. BG had higher initial and max INR, initial aPTT, and lower min PLT and min Fib compared to NBG. ROC analyses revealed that platelet count \u3c130 \u3e× 109/L, fib level2 discriminated BG from NBG. Conclusions Laboratory evidence of coagulopathy is universal in HIE babies undergoing TH. Transfusion strategies to maintain PLT counts \u3e130 × 109/L, fib level \u3e1.5 g/L, and INRpopulation

Neonatal neurobehavioral abnormalities and MRI brain injury in encephalopathic newborns treated with hypothermia

Background Neonatal Encephalopathy (NE) is a prominent cause of infant mortality and neurodevelopmental disability. Hypothermia is an effective neuroprotective therapy for newborns with encephalopathy. Post-hypothermia functional–anatomical correlation between neonatal neurobehavioral abnormalities and brain injury findings on MRI in encephalopathic newborns has not been previously described. Aim To evaluate the relationship between neonatal neurobehavioral abnormalities and brain injury on magnetic resonance imaging (MRI) in encephalopathic newborns treated with therapeutic hypothermia. Study design Neonates with hypoxic ischemic encephalopathy (HIE) referred for therapeutic hypothermia were prospectively enrolled in this observational study. Neurobehavioral functioning was assessed with the NICU network neurobehavioral scale (NNNS) performed at target age 14 days. Brain injury was assessed by MRI at target age 7–10 days. NNNS scores were compared between infants with and without severe MRI injury. Subjects & outcome measures Sixty-eight term newborns (62% males) with moderate to severe encephalopathy underwent MRI at median 8 days (range 5–16) and NNNS at median 12 days of life (range 5–20). Fifteen (22%) had severe injury on MRI. Results Overall Total Motor Abnormality Score and individual summary scores for Non-optimal Reflexes and Asymmetry were higher, while Total NNNS Z-score across cognitive/behavioral domains was lower (reflecting poorer performance) in infants with severe MRI injury compared to those without (p \u3c 0.05). Conclusions Neonatal neurobehavioral abnormalities identified by the NNNS are associated with MRI brain injury in encephalopathic newborns post-hypothermia. The NNNS can provide an early functional assessment of structural brain injury in newborns, which may guide rehabilitative therapies in infants after perinatal brain injury

Should therapeutic hypothermia be offered to babies with mild neonatal encephalopathy in the first 6 h after birth?

Infants with moderate to severe neonatal encephalopathy (NE) benefit significantly from therapeutic hypothermia, with reduced risk of death or disability. However, the need for therapeutic hypothermia for infants with milder NE remains unclear. It has been suggested that these infants should not be offered therapeutic hypothermia as they may not be at risk for adverse neurodevelopmental outcome and that the balance of risk against potential benefit is unknown. Several key questions need to be answered including first, whether one can define NE in the first 6 h after birth so as to accurately distinguish infants with brain injury who may be at risk for adverse neurodevelopmental consequences. Second, will treatment of infants with mild NE with therapeutic hypothermia improve or even worsen neurological outcomes? Although alternate treatment protocols for mild NE may be feasible, the use of the current approach combined with rigorous avoidance of hyperthermia and initiation of hypothermia as early as possible after birth may promote optimal outcomes. Animal experimental data support the potential for greater benefit for mild HIE compared with moderate to severe HIE. This review will summarize current knowledge of mild NE and the challenges to a trial in this population

The MHz-peaked radio spectrum of the unusual γ-ray source PMN J1603–4904

Context. The majority of bright extragalactic γ-ray sources are blazars. Only a few radio galaxies have been detected by Fermi/LAT. Recently, the GHz-peaked spectrum source PKS 1718–649 was confirmed to be γ-ray bright, providing further evidence for the existence of a population of γ-ray loud, compact radio galaxies. A spectral turnover in the radio spectrum in the MHz to GHz range is a characteristic feature of these objects, which are thought to be young due to their small linear sizes. The multiwavelength properties of the γ-ray source PMN J1603–4904 suggest that it is a member of this source class. Aims. The known radio spectrum of PMN J1603–4904 can be described by a power law above 1 GHz. Using observations from the Giant Metrewave Radio Telescope (GMRT) at 150, 325, and 610 MHz, we investigate the behavior of the spectrum at lower frequencies to search for a low-frequency turnover. Methods. Data from the TIFR GMRT Sky Survey (TGSS ADR) catalog and archival GMRT observations were used to construct the first MHz to GHz spectrum of PMN J1603–4904. Results. We detect a low-frequency turnover of the spectrum and measure the peak position at about 490 MHz (rest-frame), which, using the known relation of peak frequency and linear size, translates into a maximum linear source size of ~1.4 kpc. Conclusions. The detection of the MHz peak indicates that PMN J1603–4904 is part of this population of radio galaxies with turnover frequencies in the MHz to GHz regime. Therefore it can be considered the second confirmed object of this kind detected in γ-rays. Establishing this γ-ray source class will help to investigate the γ-ray production sites and to test broadband emission models

Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection

<p>Abstract</p> <p>Background</p> <p>Sex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected with <it>Klebsiella pneumoniae</it>, and 2) the phagocytic ability of macrophages from these mice.</p> <p>Methods</p> <p>Male and female C57BL/6 mice were exposed to O₃or to filtered air (FA) (control) and then infected intratracheally with <it>K. pneumoniae </it>bacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen <it>in vivo </it>was investigated after 1 h.</p> <p>Results</p> <p>1) Both male and female mice exposed to O₃are significantly more susceptible to <it>K. pneumoniae </it>infection than mice treated with FA; 2) although females appeared to be more resistant to <it>K. pneumoniae </it>than males, O₃exposure significantly increased the susceptibility of females to <it>K. pneumoniae </it>infection to a greater degree than males; 3) alveolar macrophages from O₃-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O₃-dependent reduction in phagocytic ability is greater in female mice.</p> <p>Conclusion</p> <p>O₃exposure reduces the ability of mice to survive <it>K. pneumoniae </it>infection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.</p

The unusual multiwavelength properties of the gamma-ray source PMNJ1603−4904

Context. We investigate the nature and classification of PMNJ1603−4904, a bright radio source close to the Galactic plane, which is associated with one of the brightest hard-spectrum gamma-ray sources detected by Fermi/LAT. It has previously been classified as a low-peaked BL Lac object based on its broadband emission and the absence of optical emission lines. Optical measurements, however, suffer strongly from extinction and the absence of pronounced short-time ga,,a-ray variability over years of monitoring is unusual for a blazar. Aims. In this paper, we are combining new and archival multiwavelength data of PMNJ1603−4904 in order to reconsider the classification and nature of this unusual gamma-ray source. Methods. For the first time, we study the radio morphology of PMNJ1603−4904 at 8.4GHz and 22.3GHz, and its spectral properties on milliarcsecond scales, based on VLBI observations from the TANAMI program. We combine the resulting images with multiwavelength data in the radio, IR, optical/UV, X-ray, and gamma-ray regimes. Results. PMNJ1603−4904 shows a symmetric brightness distribution at 8.4GHz on milliarcsecond scales, with the brightest, and most compact component in the center of the emission region. The morphology is reminiscent of a Compact Symmetric Object (CSO). Such objects, thought to be young radio galaxies, have been predicted to produce gamma-ray emission but have not been detected as a class by the Fermi gamma-ray telescope so far. Sparse (u,v)-coverage at 22.3GHz prevents an unambiguous modeling of the source morphology at this higher frequency. Moreover, infrared measurements reveal an excess in the spectral energy distribution (SED), which can be modeled with a blackbody with a temperature of about 1600K, and which is usually not present in blazar SEDs. Conclusions. The TANAMI VLBI data and the shape of the broadband SED challenge the current blazar classification of one of the brightest gamma-ray sources in the sky. PMNJ1603−4904 seems to be either a highly peculiar BL Lac object or a misaligned jet source. In the latter case, the intriguing VLBI structure opens room for a possible classification of PMNJ1603−4904 as a gamma-ray bright CSO

Search for Neutral Higgs Bosons of the Minimal Supersymmetric Standard Model in e+e- Interactions at \sqrt{s} = 189 GeV

A search for the lightest neutral scalar and neutral pseudoscalar Higgs bosons in the Minimal Supersymmetric Standard Model is performed using 176.4 pb^-1 of integrated luminosity collected by L3 at a center-of-mass energy of 189 GeV. No signal is observed, and the data are consistent with the expected Standard Model background. Lower limits on the masses of the lightest neutral scalar and pseudoscalar Higgs bosons are given as a function of tan(beta). Lower mass limits for tan(beta)>1 are set at the 95% confidence level to be m_h > 77.1 GeV and m_A > 77.1 GeV