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Infection remains the primary cause of death in extremely-low-birth-weight infants (ELBWIs). Alpha 1 acid glycoprotein (α1AG), an acute-phase protein, has been shown to be elevated in sporadic cases of septic ELBWIs prior to abnormal clinical signs. To delineate the roles of inflammation, delivery, and feeding in postnatal α1AG changes in ELBWIs, 75 ELBWIs of 26.5 ± 2.2 weeks of gestation born between May 2011 and August 2017 were retrospectively studied. The dependence of α1AG levels obtained on days 0–5 on the clinical variables was examined by incorporating interactions with age, followed by estimations of regression coefficients between clinical variables and α1AG levels at the early and late postnatal ages, defined by their standard deviation. Chorioamnionitis (p < 0.001), funisitis (p = 0.045), vaginal delivery (p = 0.025), enteral feeding (p = 0.022), and probiotics (p = 0.005) were associated with early α1AG elevations. Hypertensive disorder of pregnancy (p < 0.001) and gestational age (p = 0.001) were associated with late α1AG elevation; premature rupture of membranes (p < 0.001), funisitis (p = 0.021), body weight z-scores (p < 0.001), and enteral feeding (p = 0.045) were associated with late α1AG reduction. Postnatal α1AG changes in ELBWIs were associated with variables representative of age, growth, delivery, inflammation, and enteral feeding, potentially reflecting the process of sensitization to extrinsic microbes in utero, at birth, and thereafter. [ABSTRACT FROM AUTHOR]

OBJECTIVE. This study investigated the developmental changes in blood flow in each cerebral artery among infants with and without periventricular leukomalacia (PVL), to elucidate the time of onset of PVL. METHODS. Eight of 67 low birth weight infants were diagnosed through ultrasonography as having PVL with cyst formation. The mean cerebral blood flow velocities (CBFVs) in the anterior cerebral artery, middle cerebral arteries (MCAs), posterior cerebral arteries (PCAs), internal carotid arteries (ICAs), and basilar artery were measured with Doppler ultrasonography at postnatal days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, 56, and 70. Four of 8 infants with cyst formation and 1 of 59 infants without cyst formation developed cerebral palsy. RESULTS. The mean CBFVs of infants with PVL were significantly lower in the anterior cerebral artery (days 14-70), the right MCA (days 14-70), the left MCA (days 14-70), the right PCA (days 7-70), the left PCA (days 5-70), the right ICA (days 7-70), the left ICA (days 7-70), and the basilar artery (days 14 and 28-70). The CBFVs in all arteries were also lower among those with PVL than among intact infants on day 0. The CBFVs increased postnatally in the PCAs of infants with intact brains, whereas they remained unchanged after day 14 or 21 among infants with PVL. There was a significant difference in the prevalence of cerebral palsy between the 2 groups. CONCLUSIONS. We suggest that the total cerebral blood supply is decreased in cases of cystic PVL and that this reduction occurs just after birth, in a defined sequence, in the cerebral arteries. We conclude that the insult resulting in PVL might occur close to the time of birth. www.pediatrics.org/cgi/doi/10.1542/ peds.2004-1719 doi:10.1542/peds.2004-1719 Key Words periventricular leukomalacia, cerebral blood flow velocity, cerebral ischemia, transcranial ultrasonography Abbreviations PVL--periventricular leukomalacia CBFV--cerebral blood flow velocity PCA--posterior cerebral artery ACA--anterior cerebral artery MCA--middle cerebral artery BA--basilar artery ICA--internal carotid artery CP--cerebral palsy, PERIVENTRICULAR LEUKOMALACIA (PVL) is now considered the principal form of brain injury among preterm infants. PVL among very low birth weight infants is the major reason for their increased risk [...]

Metamorphic P–T conditions, monazite chemical ages and zircon U–Pb ages from the gneisses exposed in the Oki belt, Japan, were integrated to unravel the multi‐stage metamorphic history of the belt. Microstructural observations combined with obtained P–T conditions and metamorphic ages reveal three distinct stages of metamorphism: M1, M2 and M3. The M1 stage occurred c. 1.85 Ga with high‐T granulite‐facies metamorphism (793–803°C and 9.8–12.3 kbar and 738–755°C and 9.1–12.0 kbar in the southwestern and southeastern Oki gneisses, respectively). The age of the M1 stage is well recorded in monazites included in large garnet porphyroblasts and low Th/U metamorphic rims in zircons from the Oki gneisses. The M1 metamorphism was overprinted by c. 230 Ma metamorphism (M2), which occurred at granulite‐facies conditions (817–829°C and 9.0–10.3 kbar) in the southwestern Oki gneisses and at upper amphibolite‐facies conditions (693°C and 5.3 kbar) in the southeastern Oki gneisses. Monazites in small garnets, euhedral zircons and outermost rims of zircons crystallized during this stage. The final metamorphism occurred as retrograde amphibolite‐facies recrystallization (M3) at conditions of 558–638°C and 3.7–4.8 kbar. The inherited cores in zircons yield ages from Paleoarchean to Paleoproterozoic but lack Palaeozoic ages. The detrital zircon distribution and the Paleoproterozoic metamorphic event in the Oki belt support the idea that the Oki gneisses are fragments of a Precambrian terrane rather than Palaeozoic sediments derived from the terrane. Combined with previous studies, we concluded that the c. 1.85 Ga M1 high‐T granulite‐facies metamorphism in the Oki belt could be related to that of the Jiao‐Liao‐Ji belt in the eastern North China block via the northern Gyeonggi and Nangrim Massifs on the Korean Peninsula, whereas the c. 250–230 Ma M2 stage could be associated with collision between the North and South China blocks. The Oki belt geologically corresponds to the northern Gyeonggi Massif in South Korea due to their similar Paleoproterozoic and Triassic tectonothermal events. [ABSTRACT FROM AUTHOR]

Long-term data about the incidence of late adverse radiation effects (AREs) in pediatric brain arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS) are lacking. This study addresses the incidence of late AREs, including cyst formation (CF), chronic encapsulated hematoma (CEH), and radiation-induced tumor, in pediatric patients with AVM treated with GKRS. This is a single-institutional study involving pediatric patients with AVM who underwent GKRS between 1991 and 2014. Among 201 pediatric patients with AVM (age ≤15 years), 189 who had at least 12 months of follow-up were assessed in this study. The median treatment volume was 2.2 cm3, and the median marginal dose was 20 Gy. The mean follow-up period was 136 months. During the follow-up period, symptomatic radiation-induced perilesional edema was found in 5 patients (3%), CFs in 7 patients (4%), CEHs in 7 patients (4%), and radiation-induced tumors in 2 patients (1%). The cumulative incidences of late AREs including CF, CEH, and radiation-induced tumor were 1.2% at 5 years, 5.2% at 8 years, 6.1% at 10 years, 7.2% at 15 years, and 17.0% at 20 years. In the multivariate analysis, treatment volume alone was a significant factor for late AREs (P < 0.001; hazard ratio, 1.111). GKRS is a reasonable treatment option for pediatric AVMs to prevent future intracranial hemorrhages, particularly in the eloquent regions. However, considerable attention should be paid to late AREs such as CFs, CEHs, and radiation-induced tumors because of longer life expectancy in pediatric patients. [ABSTRACT FROM AUTHOR]

Little is known about long-term outcomes for pediatric brain arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS). This study investigated annual hemorrhage rates and nidus obliteration rates, and the factors affecting them, in pediatric AVMs treated with GKRS. We examined 189 pediatric AVM patients (age ≤15 years) who underwent GKRS and had at least 12 months of follow-up. The Spetzler-Martin (S-M) grade was I in 29 patients (15%), II in 57 (30%), III in 82 (43%), IV in 16 (9%), and V in 5 (3%). The median treatment volume was 2.2 cm3, and the median marginal dose was 20 Gy. The mean follow-up period was 136 months. During a cumulative latency period to nidus obliteration of 813 years, 23 hemorrhages occurred, resulting in an annual post-GKRS hemorrhage rate of 2.8%. The cumulative hemorrhage rates after GKRS were 3.3%, 8.5%, and 11.9% at 3, 5, and 10 years, respectively. Higher S-M grade was significantly associated with intracranial hemorrhages during the latency period (P < 0.001). The actuarial nidus obliteration rates with repeated GKRS were 64% and 81% at 5 and 10 years, respectively. Absence of pre-GKRS embolization (P = 0.023) and higher marginal dose (P = 0.029) were significant factors predicting nidus obliteration. GKRS is a reasonable treatment option in pediatric AVMs to prevent future hemorrhages. Because higher S-M grade AVMs are more likely to hemorrhage during the latency period, a combined therapy with endovascular embolization should be considered to prevent AVM rupture. [ABSTRACT FROM AUTHOR]

Background: Inflammatory cytokines are implicated in the pathogenesis of perinatal hypoxia-ischemia (HI). The influence of hypothermia (HT) on cytokines after HI is unclear. Our aim was to assess in a piglet asphyxia model, under normothermic (NT) and HT conditions: (i) the evolution of serum cytokines over 48 h and (ii) cerebrospinal fluid (CSF) cytokine levels at 48 h; (iii) serum pro/anti-inflammatory cytokine profile over 48 h and (iv) relation between brain injury measured by magnetic resonance spectroscopy (MRS) and brain TUNEL positive cells with serum cytokines, serum pro/anti-inflammatory cytokines and CSF cytokines.Methods: Newborn piglets were randomized to NT (n = 5) or HT (n = 6) lasting 2-26 h after HI. Serum samples were obtained 4-6 h before, during and at 6-12 h intervals after HI; CSF was obtained at 48 h. Concentrations of interleukin (IL)-1β, -4, -6, -8, -10 and TNF-α were measured and pro/anti-inflammatory status compared between groups. White matter and thalamic voxel lactate/N-acetyl aspartate (Lac/NAA) (a measure of both oxidative metabolism and neuronal loss) were acquired at baseline, after HI and at 24 and 36 h.Results: Lac/NAA was reduced at 36 h with HT compared to NT (p = 0.013 basal ganglia and p = 0.033 white matter). HT showed lower serum TNF-α from baseline to 12 h (p < 0.05). Time-matched (acquired within 5 h of each other) serum cytokine and MRS showed correlations between Lac/NAA and serum IL-1β and IL-10 (all p < 0.01). The pro/anti-inflammatory ratios IL-1β/IL-10, IL-6/IL-10, IL-4/IL-10 and IL-8/IL-10 were similar in NT and HT groups until 36 h (24 h for IL-6/IL-10); after this, 36 h pro/anti-inflammatory cytokine ratios in the serum were higher in HT compared to NT (p < 0.05), indicating a pro-inflammatory cytokine surge after rewarming in the HT group. In the CSF at 48 h, IL-8 was lower in the HT group (p < 0.05). At 48 h, CSF TNF-α correlated with Lac/NAA (p = 0.02) and CSF IL-8 correlated with white matter TUNEL positive cell death (p = 0.04).Conclusions: Following cerebral HI, there was a systemic pro-inflammatory surge after rewarming in the HT group, which is counterintuitive to the putative neuroprotective effects of HT. While serum cytokines were variable, elevations in CSF inflammatory cytokines at 48 h were associated with MRS Lac/NAA and white matter cell death. [ABSTRACT FROM AUTHOR]

Background Persistent patent ductus arteriosus (PDA) is a frequent complication in preterm infants. Single nucleotide polymorphisms (SNP) in several genes, including angiotensin II receptor, type 1 ( AGTR1), transcription factor AP-2 beta ( TFAP2B) and tumor necrosis factor receptor-associated factor 1 ( TRAF1), have been reported to be associated with PDA in preterm infants. The aim of this study was to evaluate the relationships between PDA in preterm infants and polymorphisms in AGTR1, TFAP2B and TRAF1 in the Japanese population. Methods The subjects consisted of 107 preterm infants with gestational age <32 weeks. Extremely low-birthweight infants were treated with prophylactic indomethacin during the first 24 h after birth. Five SNP, namely, rs5186 in AGTR1, rs987237 and rs6930924 in TFAP2B, and rs1056567 and rs10985070 in TRAF1, were genotyped using TaqMan SNP genotyping assays. Results There were no significant differences in the distributions of the genotypes and allele frequencies of all studied SNP between the PDA group (n = 46) and the non-PDA group (n = 61). Conclusions There were no significant associations between the studied SNP and the incidence of PDA in Japanese preterm infants. These SNP may not be clinically important predisposing factors for PDA in Japanese preterm infants. [ABSTRACT FROM AUTHOR]

Na+/H+ exchanger ( NHE) blockade attenuates the detrimental consequences of ischaemia and reperfusion in myocardium and brain in adult and neonatal animal studies. Our aim was to use magnetic resonance spectroscopy ( MRS) biomarkers and immunohistochemistry to investigate the cerebral effects of the NHE inhibitor, methyl isobutyl amiloride ( MIA) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged < 24 h) underwent transient global cerebral hypoxia-ischaemia and were randomized to (i) saline placebo; or (ii) 3 mg/kg intravenous MIA administered 10 min post-insult and 8 hourly thereafter. Serial phosphorus-31 (31P) and proton (1H) MRS data were acquired before, during and up to 48 h after hypoxia-ischaemia and metabolite-ratio time-series Area under the Curve ( AUC) calculated. At 48 h, histological and immunohistochemical assessments quantified regional tissue injury. MIA decreased thalamic lactate/N-acetylaspartate and lactate/creatine AUCs (both p < 0.05) compared with placebo. Correlating with improved cerebral energy metabolism, transferase mediated biotinylated d-UTP nick end-labelling ( TUNEL) positive cell density was reduced in the MIA group in cerebral cortex, thalamus and white matter (all p < 0.05) and caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate nucleus (both p < 0.05). Microglial activation was reduced in pyriform and midtemporal cortex (both p < 0.05). Treatment with MIA starting 10 min after hypoxia-ischaemia was neuroprotective in this perinatal asphyxia model. [ABSTRACT FROM AUTHOR]

Abstract: This paper outlines the CHIME (chemical Th–U-total Pb isochron method) dating method, which is based on precise electron microprobe analyses of Th, U and Pb in Th- and U-bearing accessory minerals such as monazite, xenotime, zircon and polycrase. The age-mapping technique that is applicable to young monazite and zircon is also described. CHIME dating consists of analyzing multiple spots within homogeneous age domains that show sufficient compositional variation, and then these data are used to construct a “pseudo-isochron” from which an age can be obtained via regression. This method, when coupled with discrimination of possibly concordant age data by chemical criteria such as the (Ca+Si)/(Th+U+Pb+S) ratio for monazite and Ca and S contents for zircon, has the potential advantage of significant precision, and the ability to work with minerals that have a significant initial common Pb component. This technique can identify two or more homogeneous domains that are separated by age gaps smaller than the error on individual spot age analysis. Many features that are insignificant in major element analysis can have major impact in the acquisition of trace element data. Critical factors include the roles of collimator slit, detector gas, background estimation, accelerating voltage, probe current, X-ray interferences and count rate in affecting the accuracy, and a way to apply the Th and U interference correction without pure Th- and U-oxides or synthesized pure ThSiO4. The age-mapping procedure for young monazite and zircon includes acquiring PbMα (or PbMβ) intensity of individual pixels with multiple spectrometers, correcting background with background maps computed from a measured background intensity by the intensity relationships determined in advance of the measurement, calibrating of intensity with standards and calculating of ages from the Th, U and Pb concentrations. This technique provides age maps that show differences in age domains on the order of 20 Ma with in monazite as young as 100 Ma. The effect of sample damage by irradiation of intense and prolonged probe measurement is also described. [Copyright &y& Elsevier]

The chemical Th-U-total Pb isochron method (CHIME) has been applied to determine the ages of monazite grains from metasediments of greenscshist-amphibolite facies in the Altai orogen, northwest China. The area of distribution of these metamorphic rocks is divided into the Permian (261–268 Ma) central-western and Devonian (377–382 Ma) eastern units on the basis of their metamorphic ages. The Devonian CHIME ages are consistent with the Pb–Pb ages of granitoid in the eastern unit, and support the idea that emplacement of the granitoids was synchronous with regional metamorphism at deep levels. The Permian metamorphic ages (the present study) and igneous ages previously reported from the central-western unit can be interpreted in terms of subduction of crustal material and oceanic plate, and rapid exhumation. [ABSTRACT FROM AUTHOR]

Carbon (25–30 nm in thickness) is the most common coating material used in the electron probe microanalysis (EPMA) of geological samples. A gold coating is also used in special cases to reduce the surface damage by electron bombardment. Monte Carlo simulations have been performed for monazite with a 25 nm carbon and a 10 nm gold coating to understand the effect of a coating film in quantitative EPMA at E0= 15 keV and 25 keV. Simulations showed that carbon-coated monazite gave the same depth distribution of the generated X-rays in the monazite as uncoated monazite, whilst gold-coated monazite gave a distorted depth distribution. A 10 nm gold coating was 1.06 (15 keV) and 1.05 (25 keV) times higher in k-ratio between monazite and pure thorium than a 25 nm carbon coating at an X-ray take-off angle of 40 degrees. Thus, a 10 nm gold coating is a possible factor contributing to inaccuracy in quantitative EPMA of monazite, while a 25 nm carbon coating does not have a significant effect. [ABSTRACT FROM AUTHOR]