Aim
We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify cognitive performance delay at 2 years in a large cohort of infants born at term.
Method
We conducted ...a retrospective study of infants born at term at risk of neurodevelopmental impairments assessed using the HINE between 3 and 12 months post‐term age and compared them with a cohort of typically developing infants born at term. All infants performed a neurodevelopmental assessment at 2 years of age using the Mental Development Index (MDI) of the Bayley Scales of Infant Development, Second Edition; the presence of cerebral palsy (CP) was also reported. The infants were classified as being cognitively normal/mildly delayed or significantly delayed (MDI < 70). The predictive validity of HINE scores for significantly delayed cognitive performance, in infants with and without CP, was calculated using specific cut‐off scores according to age at assessment.
Results
A total of 446 at‐risk and 235 typically developing infants (345 males, 336 females; mean SD gestational age 38.7 weeks 1.4, range 37–43 weeks) were included. Of the at‐risk infants, 408 did not have CP at 2 years; 243 had a normal/mild delayed MDI and 165 had an MDI less than 70. Of the at‐risk infants, 38 developed CP. HINE scores showed a good sensitivity and specificity, mainly after 3 months, for identifying significantly delayed cognitive performance in infants without CP. In those with CP, the score was associated with their cognitive performance. The comparison group had the highest HINE scores.
Interpretation
The HINE provides evidence about the risk of delayed cognitive performance at age 2 years in infants born at term with and without CP.
RESUMEN
Examen neurológico infantil de Hammersmith en bebés nacidos a término: su uso para predecir otras condiciones además de la parálisis cerebral
Objetivo
Valoramos la capacidad del examen neurológico infantil de Hammersmith (HINE) para identificar el retraso en el rendimiento cognitivo a los 2 años en una cohorte grande de bebés nacidos a término.
Método
Realizamos un estudio retrospectivo de bebés nacidos a término con riesgo de trastornos del desarrollo neurológico evaluados mediante el HINE entre los 3 y los 12 meses de edad postérmino y los comparamos con una cohorte de bebés nacidos a término con un desarrollo típico. Todos los bebés realizaron una evaluación del desarrollo neurológico a los 2 años de edad utilizando el Índice de Desarrollo Mental (MDI) de las Escalas de Desarrollo Infantil de Bayley, Segunda Edición; también se informó la presencia de parálisis cerebral (PC). Los bebés se clasificaron como cognitivamente normales/levemente con retreaso o significativamente con retraso (MDI < 70). La validez predictiva de las puntuaciones HINE para el rendimiento cognitivo con retraso significativo, en bebés con y sin parálisis cerebral, se calculó utilizando puntuaciones de corte específicas según la edad en la evaluación.
Resultados
Se incluyeron un total de 446 lactantes en riesgo y 235 con desarrollo normal (345 varones, 336 mujeres; edad gestacional media DE 38,7 semanas 1,4, rango de 37 a 43 semanas). De los lactantes en riesgo, 408 no tenían parálisis cerebral a los 2 años; 243 tenían un MDI con retraso normal/leve y 165 tenían un MDI inferior a 70. De los bebés en riesgo, 38 desarrollaron PC. Las puntuaciones HINE mostraron una buena sensibilidad y especificidad, principalmente después de 3 meses, para identificar un rendimiento cognitivo severo en lactantes sin PC. En aquellos con PC, la puntuación se asoció con su rendimiento cognitivo. El grupo de comparación tuvo las puntuaciones HINE más altas.
Interpretación
El HINE proporciona evidencia sobre el riesgo de retraso en el rendimiento cognitivo a los 2 años de edad en bebés nacidos a término con y sin parálisis cerebral.
This original article is commented on by Cao and Huang on pages 813‐814 of this issue.
Abstract
At Mount Etna volcano, the focus point of persistent tectonic extension is represented by the Summit Craters. A muographic telescope has been installed at the base of the North-East Crater ...from August 2017 to October 2019, with the specific aim to find time related variations in the density of volcanic edifice. The results are significant, since the elaborated images show the opening and evolution of different tectonic elements; in 2017, a cavity was detected months before the collapse of the crater floor and in 2018 a set of underground fractures was identified, at the tip of which, in June 2019, a new eruptive vent started its explosive activity, still going on (February, 2020). Although this is the pilot experiment of the project, the results confirm that muography could be a turning point in the comprehension of the plumbing system of the volcano and a fundamental step forward to do mid-term (weeks/months) predictions of eruptions. We are confident that an increment in the number of telescopes could lead to the realization of a monitoring system, which would keep under control the evolution of the internal dynamic of the uppermost section of the feeding system of an active volcano such as Mount Etna.
Polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) represent typical myeloproliferative neoplasms (MPN), usually characterized by specific somatic driver ...mutations (JAK2 V617F, CALR and MPL). JAK2 46/1 haplotype and telomerase reverse transcriptase gene (TERT) rs2736100 A>C single nucleotide polymorphism (SNP) could represent a large fraction of the genetic predisposition seen in MPN. The rs10974944 C>G SNP, tagging the JAK2 46/1 haplotype, and the TERT rs2736100 A>C SNP were genotyped in 529 MPN patients with known JAK2 V617F, CALR and MPL status, and 433 controls. JAK2 46/1 haplotype strongly correlated to JAK2 V617F‐positive MPN and, to a lesser extent, CALR‐positive MPN. The TERT rs2736100 A>C SNP strongly correlated to all MPN, regardless of the phenotype (PV, ET or PMF) and major molecular subtype (JAK2 V617F‐ or CALR‐positive). While both variants have a significant contribution, they have nuanced consequences, with JAK2 46/1 predisposing essentially to JAK2 V617F‐positive MPN, and TERT rs2736100 A>C having a more general, non‐specific effect on all MPN, regardless of phenotype or major molecular subtype.
Fuel cells could become the main power source for small general aviation aircraft or could replace APU and internal sub-systems on larger aircraft, to obtain all-electric or more-electric air ...vehicles. There are several potential advantages of using such a power source, that range from environmental and economic issues to performance and operability aspects. A preliminary design is reported. Also, the paper contains a description of testing activities related to experimental flights of an all-electric general aviation aircraft fueled by hydrogen. Great importance has been given to the testing phase of the prototype and examples of each testing stage are shown ranging from the single components to the final test flights. During the 6 experimental flights a rotation speed of 84 km/h was obtained in 184 m of taxi at power of 35 kW. Level flight was attained at 135 km/h and endurance of 39 min by mean of only a fuel cell power setting (speed world record for the FAI Sporting Code Category C – airplane).
Thermal neutron scattering is a powerful tool to directly probe protein internal motions. Here, we report an incoherent neutron scattering study of the effect of glycerol-, disaccharide- CO(NH
2
)
2
...-aqueous mixtures on the internal dynamics of lysozyme powder. Mean-square displacement of amplitude motions as a function of temperature was evaluated. We showed the complex interdependence between the motions of the protein, water of hydration, and co-solvent. Analysis of data gives access to the geometry of the observed motions. Then the crucial role of the solvent mobility to activate thermal fluctuations is proposed.
Lactoferrin is a mammalian milk glycoprotein involved in innate immunity. Recent data show that bovine lactoferrin (bLF) prevents late-onset sepsis in preterm very low birth weight (VLBW) neonates.
...This is a secondary analysis of data from a multicenter randomized controlled trial where preterm VLBW neonates randomly received bLF (100 mg/day; group A1), bLF + Lactobacillus rhamnosus GG (10(6) colony-forming units per day; group A2), or placebo (group B) for 6 weeks. Here we analyze the incidence rates of fungal colonization, invasive fungal infection (IFI), and rate of progression from colonization to infection in all groups.
This study included 472 neonates whose clinical, nutritional, and demographical characteristics were similar. Overall, the incidence of fungal colonization was comparable (17.6%, 16.6%, and 18.5% in A1, A2, and B, respectively; P = .89 A1 and .77 A2). In contrast, IFIs were significantly decreased in A1 and A2 (0.7% and 2.0%, respectively) compared with B (7.7%; P = .002 A1 and .02 A2), and this was significantly true both in <1000 g (0.9% A1 and 5.6% A2, vs 15.0%) and in 1001 to 1500 g infants (0% and 0% vs 3.7%). The progression rate colonization-infection was significantly lower in the bLF groups: 3.7% (A1) and 12% (A2), vs 41.9%; P < .001 (A1) and P = .02 (A2). No IFI-attributable deaths occurred in the treatment groups, versus 2 in placebo. No adverse effects or intolerances occurred.
Prophylactic oral administration of bLF reduces the incidence of IFI in preterm VLBW neonates. No effect is seen on colonization. The protective effect on IFI is likely due to limitation of ability of fungal colonies to progress toward invasion and systemic disease in colonized infants.
We study the structure and linear viscoelasticity of interacting polymer nanocomposites based on mixtures of poly(ethylene oxide) and fumed silica particles. The filler is dispersed within the ...polymer using two different techniques which lead to different dispersion states. The analysis of the dynamic response of our systems highlights the formation of a stress-bearing network above a critical volume fraction, Φc. Extending a two-phase model used to describe weakly interacting systems, we show that above Φc the melt-state elasticity of the composites arises from the independent contributions of a polymer–particle network and a viscous matrix. We also find that, although Φc depends on the initial state of dispersion, the network elasticity scales with volume fraction following a universal power-law, with an exponent ν ≈ 1.8. Such a scaling law has been recently predicted for the stress-bearing mechanism governed by polymer-mediated interactions.
The aim of this review is to highlight the advances in the field of heme oxygenase-1 (HO-1) inhibitors over the past years, particularly from a medicinal chemistry point of view; progresses made in ...the field strongly helped to clarify physiological roles of the heme oxygenase (HO) system. HO is a family of ubiquitously expressed enzymes which regulate the regiospecific catabolism of heme leading to the formation of equimolar amounts of carbon monoxide (CO), ferrous iron (Fe⁺⁺), and biliverdin. HO exists in two distinct, catalytically active isoforms: HO-1 and HO-2. HO-1 is an inducible 32-kDa protein, while HO-2 is a constitutively synthesized 36-kDa protein and generally is unresponsive to any of the inducers of HO-1. A third isoform, HO-3, is still an elusive protein. The HO system, along with its catabolism products, is involved in a variety of crucial physiological functions, including cytoprotection, inflammation, anti-oxidative effects, apoptosis, neuro-modulation, immune-modulation, angiogenesis, and vascular regulation. The use of selective HO inhibitors is a very important tool to clarify the role of the HO system and the mechanisms underlying its physiological effects and pathological involvement; due to the inducible nature of HO-1, selective inhibition of HO-1 isoform is generally preferable. Notably, HO-1 inhibitors may be also beneficial in therapeutic applications and have been mainly studied for treatment of hyperbilirubinemia and certain types of cancer. Historically, the first molecules used as non selective HO-1 inhibitors were metalloporphyrins (Mps). The subsequent development of the imidazole-dioxolane derivatives afforded the first generation of non-porphyrin based, isozyme selective HO-1 inhibitors.
A procedure for the characterization of low velocity impact damage and its effect on residual tensile and buckling behaviour of composite structures is presented. A simplified analytical method is ...used to enhance the damage simulation and a degradation model is introduced in the subsequent finite element analysis. Different degradation coefficients are defined for three impact energy stages. Two different types of analysis are performed using MD.Nastran software: the non-linear progressive failure analysis to estimate the residual tensile strength and the linear analysis to predict the critical uniaxial and shear buckling loads after impact. Tensile and buckling experiments are used to validate the present methodology. A good correlation is obtained for all the cases under investigation.
The microvasculature plays a key role in tissue perfusion and exchange of gases and metabolites. In this study we use human blood vessel organoids (BVOs) as a model of the microvasculature. BVOs ...fully recapitulate key features of the human microvasculature, including the reliance of mature endothelial cells on glycolytic metabolism, as concluded from metabolic flux assays and mass spectrometry-based metabolomics using stable tracing of
C-glucose. Pharmacological targeting of PFKFB3, an activator of glycolysis, using two chemical inhibitors results in rapid BVO restructuring, vessel regression with reduced pericyte coverage. PFKFB3 mutant BVOs also display similar structural remodelling. Proteomic analysis of the BVO secretome reveal remodelling of the extracellular matrix and differential expression of paracrine mediators such as CTGF. Treatment with recombinant CTGF recovers microvessel structure. In this work we demonstrate that BVOs rapidly undergo restructuring in response to metabolic changes and identify CTGF as a critical paracrine regulator of microvascular integrity.
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