Effects of MK-801 and Phenytoin on Flurothyl-Induced Seizures During Development

Summary We determined the effects of the N-methyl-Daspartate (NMDA) receptor blocker MK-801 (0.05, 0.1, and 0.5 mg/kg intraperitoneally, i.p.) and phenytoin (PHT, 5, 10, and 20 mg/kg i.p.) on flurothyl-induced clonic and tonic-clonic seizures in 9-, 1 5, 30-, and 60-day-old male rats. Both agents had seizure-, age-, and dose-specific effects. The highest dose of MK-801 was anticonvulsant against clonic flurothyl-induced seizures only in 9- and 60-day-old rats, but suppressed tonic-clonic seizures in all ages. The lowest dose of MK-801 (0.05 mg/kg) produced significant anticonvulsant effects only in 15 day old rats. PHT did not have any effect on clonic seizures throughout development. Both doses of PHT (10 and 20 mg/kg) were anticonvulsant against tonic-clonic seizures in adult rats but not in any other age group. The results indicate that NMDA receptors play an important role in tonic-clonic flurothyl-induced seizures throughout development (especially in 15-day-old rats) and that the anticonvulsant effects of PHT may vary at different stages of brain development.     

Fast Three Dimensional Magnetic Resonance Imaging

To reduce the scan time in three-dimensional (3D) imaging, the authors consider alternative trajectories for traversing k-space. They differ from traditional 3D trajectories, such as 3DFT, in that they employ time-varying gradients allowing longer readouts and in turn a reduced scan time. Some of these trajectories reduce by an order of magnitude the number of excitations compared with 3DFT and provide flexibility for trading off signal-to-noise ratio for scan time. Other concerns are the minimum echo time and flow/motion properties. As examples, the authors show two applications: A 3D data set of the head (field of view of 30 x 30 x 7.5 cm and resolution of 1.5 x 1.5 x 1.5 mm) acquired in 56 s using a stack of spirals in 3D k-space; and a 3D movie of the heart (20 x 20 x 20 cm field of view, 2 x 2 x 2 mm resolution, and 16 time frames per cardiac cycle) acquired in 11 min using a cones trajectory.     

A Developmental Event-Related Potential Study of Picture Matching in Children, Adolescents, and Young Adults: A Replication and Extension

Event-related potentials were recorded in a developmental study of picture matching using an adaptation of Posner's (1978) letter-matching tasks. Subjects ranging in age from 6-39 were asked to decide whether two line drawings, presented sequentially, were the same or different on the basis of physical (physical identity), nominal (name identity), or categorical (category identity) criteria. The amplitude of a negativity at 400 ms (Neg400) increased as the number of dimensions on which the two line drawings differed increased. This effect held for all age groups, and was interpreted as reflecting the degree of semantic and/or physical relationship between the two pictures. However, one finding for Neg400 did suggest a qualitative difference in processing mode between the younger and older subjects. Both Neg400 and P3b latencies showed highly significant linear age trends, decreasing with increasing age. These age-related changes were interpreted as demonstrating quantitative speed of processing differences among age groups. The latencies of both Neg400 and P3b increased as the matching criteria became more complex. Moreover, P3b latency increased as the number of dimensions on which the two pictures differed increased, and this did not interact with age. Although both Neg400 and P3b showed age-related changes in scalp distribution, the fact that each was related to the experimental variables in similar fashion in all age groups suggested that they were homologous components across the age range studied. Taken as a whole, the data support continuity of information processing during these tasks across a wide age range.     

大学生性行为及性道德观发展研究

目的 了解当代大学生性行为及性道德观念的发展变化。方法 自制问卷，对全国9所高校的2000余名大学生进行调查，并用SPSS10．0对结果进行统计处理。结果 大学生性交行为发生率呈逐年上升趋势，且随年级上升而增加；大学生认可性交行为道德观的5个雏度，但各年级之间有差异；大学生边缘性行为和独自性行为发生率随年级显著上升，认可度也随年级增加而上升；大学生对同性性接触基本持排斥态度，但排斥态度则趋于下降。结论 大学生性行为和性道德随年级上升而明显变化，应加强学校教育和引导。     

Structural studies of murine I-E and human DR antigens.

The structures of murine I-E antigens from two strains of mice were compared to each other and to human DR antigens. Murine and human antigens were isolated by using allo- and xenoantiserum, respectively, and purified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The murine I-E and human DR antigens consist of two polypeptide chains designated α and β. The E_α and DR_α chains display a high degree of amino acid sequence homology as do the E_β and DR_β chains, provided a gap is inserted at position 1 of the DR_β chain. Comparison of N-terminal sequences reveals several differences between the β chains of I-E antigens from the two strains of mice. In contrast no sequence differences between the two α chains are observed. In addition, comparison of tryptic peptides examined by isoelectrofocusing reveals several differences between the two E_β chains, but not between the two E_α chains. Thus, the polymorphism of murine I-E antigens and by analogy human DR antigens, may result from structural differences in the smaller (β) chain.     

Classification of B-cells according to their differentiation status, their micro-anatomical localisation and their developmental lineage

B-lymphocytes or B-cells form a diverse and flexible repertoire of immune cells that are reactive to almost all potential pathogens by means of the production of antigen-specific immunoglobulins. They can be divided into different populations or subsets, characterised by a distinct combination of properties. These subsets are identified on the base of their differentiation status (precursor B-cells, peripheral B-cells), their localisation in the micro-anatomical compartments of the B-cell follicle (marginal zone B-cells, lymphocytic corona B-cells, follicle centre B-cells), and the developmental lineage to which they belong (B-1 cells, and B-2 or conventional B-cells). The latter classification of B-cells into B-1 cells and B-2 cells is commonly followed by immunologists, mainly in the study of mice models, while pathologists and haematologists tend to use a terminology for B-cells which refers to their localisation in the micro-anatomical compartments of the B-cell follicle and/or differentiation status. In this review, we will discuss the various subsets of B-cells and point to the similarities between the various classification systems in use.     

Morphological analysis of the cervical spinal canal,dural tube and spinal cord in normal individuals using CT myelography

To verify the conventional concept of developmental stenosis of the cervical spinal canal, we performed a morphological analysis of the relations of the cervical spinal canal, dural tube and spinal cord in normal individuals. The sagittal diameter, area and circularity of the three structures, and the dispersion of each parameter, were examined on axial sections of CT myelograms of 36 normal subjects. The spinal canal was narrowest at C4, followed by C5, while the spinal cord was largest at C4/5. The area and circularity of the cervical spinal cord were not significantly correlated with any parameter of the spinal canal nor with the sagittal diameter and area of the dural tube at any level examined, and the spinal cord showed less individual variation than the bony canal. Compression of the spinal cord might be expected whenever the sagittal diameter of the spinal canal is below the lower limit of normal, that is about 12 mm on plain radiographs. Thus, we concluded that the concept of developmental stenosis of the cervical spinal canal was reasonable and acceptable.     

The developmental paediatrician and neonatal follow-up

Recent advances in modern perinatal and neonatal intensive care have led to an increase in the survival of premature infants. This increased survival, unfortunately, has not been accompanied by an improvement in neurodevelopmental outcomes. Premature infants, especially those with an extremely low birth weight (less than 1000 g) or those born at less than 28 weeks’ gestation, are at increased risk of major disabilities and complex, ‘low severity’ dysfunctions that have significant, lasting effects on their school function, academic performance and behaviour, as well as on family function. Neonatal follow-up programs provide a number of functions to centres providing neonatal intensive care, including quality assurance and audits, research and follow-up clinical care to neonatal intensive care unit survivors and their families. The challenge for neonatal follow-up programs is to meet the often competing objectives of providing clinical services to children and their families while providing quality assurance and audits, and high-quality long-term outcome research components, given the available resources. There is also a need for ongoing research to develop and evaluate effective postdischarge intervention programs to improve the long-term outcome of prematurity and other neonatal complications. Developmental paediatricians – with their background and training in the provision of specialized health care to children and their care-givers with respect to developmental and psychosocial well-being, and in conducting developmental and behavioural disabilities research – play a valuable role in the follow-up assessment and care of neonatal intensive care unit graduates, and strengthen the multidisciplinary research groups necessary to assess long-term outcomes and the effects of perinatal and postdischarge interventions.     

L-Serine Treatment is Associated with Improvements in Behavior,EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants

Pathogenic missense variants in GRIN2A and GRIN2B may result in gain or loss of function (GoF/LoF) of the N-methyl-D-aspartate receptor (NMDAR). This observation gave rise to the hypothesis of successfully treating GRIN-related disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of ten individuals with GRIN2A- or GRIN2B-related disorders who were treated with L-serine, each within an independent n-of-1 trial. Our cohort comprises one individual with a LoF missense variant with clinical improvements confirming the above hypothesis and replicating a previous n-of-1 trial. A second individual with a GoF missense variant was erroneously treated with L-serine and experienced immediate temporary behavioral deterioration further supporting the supposed functional pathomechanism. Eight additional individuals with null variants (that had been interpreted as loss-of-function variants despite not being missense) again showed clinical improvements. Among all nine individuals with LoF missense or null variants, L-serine treatment was associated with improvements in behavior in eight (89%), in development in four (44%), and/or in EEG or seizure frequency in four (44%). None of these nine individuals experienced side effects or adverse findings in the context of L-serine treatment. In summary, we describe the first evidence that L-serine treatment may not only be associated with clinical improvements in GRIN-related disorders due to LoF missense but particularly also null variants.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01173-9.