Leukemoid Reaction and Preterm Birth: A Case Report of FIRS (Fetal Inflammatory Response Syndrome)

This article describes a case of severe hyperleukocytosis in a preterm infant with fetal inflammatory response syndrome (FIRS) associated with funisitis of umbilical cord and intrauterine inflammation. FIRS is a cause of leukocytosis in newborn, as well as leukemoid reaction in 21 trisomy, congenital leukemia, sepsis, and steroid prophylaxis. Inflammatory response syndrome is associated with high mortality, developmental impairment and complications of prematurity like intraventricular hemorrhage, chronic lung disease, periventricular leukomalacia, and sepsis.

Neuroimmune Evasion of Zika Virus to Facilitate Viral Pathogenesis

Zika virus (ZIKV), which preferentially targets neural stem and progenitor cells (NSCs) especially in developing brain, is causally associated with fetal microcephaly, intrauterine retardation, and other congenital malformations in humans. However, there are, so far, no effective drugs and vaccines against ZIKV epidemics, warranting an enhanced understanding of ZIKV biology. Immune response is essential for neuronal cells to combat viral invasion. In turn, neurotropic ZIKV has developed a complex strategy of neuroimmune evasion to facilitate viral pathogenesis, especially developmental impairment in embryonic brain. Here, we review not only overall knowledge of ZIKV-related immune responses, but also current advances in our understanding of immune evasion in ZIKV infection. We also review several specific mechanisms underlying ZIKV protein-mediated immune evasion for viral pathogenesis.

How paediatricians investigate early developmental impairment: a qualitative descriptive study

Background Early developmental impairment (EDI) is common and has many aetiologies and, therefore, potential investigations. There are several published guidelines recommending aetiological investigations, and paediatricians’ views of them varies. Little is known on the thought processes underlying clinical decisions in investigating EDI. This study aimed to describe the thought processes affecting clinical decisions on the investigation of EDI within a nationalised health care system. Methods A qualitative descriptive study using semi-structured qualitative interviews performed in person or via video link with paediatricians who see children with EDI in England. As part of the interview, a case study of a fictional disease, Cavorite deficiency, modelled on biotinidase deficiency, was given to participants with the cost of testing, incidence and likelihood it would respond to treatment. This allowed exploration of cost without encumbrance from predisposing views and training on the condition. Thematic analysis was performed by iterative approach. Where participants stated they wanted to redirect money from investigations to treatment, were that even possible, we asked which services they would like to be better funded in their area. Results Interviews were conducted with 14 consultant paediatricians: 9 Community / Neurodisability, 2 General paediatricians, and 3 Paediatric Neurologists. Two themes were identified: the value of an aetiological diagnosis to families and managing risk and probability when investigating EDI. The latter contained 4 subthemes: ‘circumspection’ involved blanket investigations chosen irrespective of phenotype and high regard for guidelines; ‘accepting appropriate risk’ involved participants choosing investigations based on clinical phenotype, recognising some aetiologies would be missed; consultants found they ‘transitioned between practices’ during their career; and ‘improved practice’ was thought possible with better evidence on how to stratify investigations based on phenotype. Services that were most frequently reported to need additional funding were therapy services, early community developmental services, management of behaviour, sleep and mental health, and educational support. Conclusions There are many factors that influence paediatricians’ choice of aetiological investigation in EDI, but clinical factors are the most important. Paediatricians want better evidence to allow them to select the right investigations for each child without a significant risk of missing an important diagnosis.

Cockayne Syndrome Group B (CSB): The Regulatory Framework Governing the Multifunctional Protein and Its Plausible Role in Cancer

Cockayne syndrome (CS) is a DNA repair syndrome characterized by a broad spectrum of clinical manifestations such as neurodegeneration, premature aging, developmental impairment, photosensitivity and other symptoms. Mutations in Cockayne syndrome protein B (CSB) are present in the vast majority of CS patients and in other DNA repair-related pathologies. In the literature, the role of CSB in different DNA repair pathways has been highlighted, however, new CSB functions have been identified in DNA transcription, mitochondrial biology, telomere maintenance and p53 regulation. Herein, we present an overview of identified structural elements and processes that impact on CSB activity and its post-translational modifications, known to balance the different roles of the protein not only during normal conditions but most importantly in stress situations. Moreover, since CSB has been found to be overexpressed in a number of different tumors, its role in cancer is presented and possible therapeutic targeting is discussed.

Absence of Thyroid Hormone Induced Delayed Dendritic Arborization in Mouse Primary Hippocampal Neurons Through Insufficient Expression of Brain-Derived Neurotrophic Factor

Thyroid hormone (TH) plays important roles in the developing brain. TH deficiency in early life leads to severe developmental impairment in the hippocampus. However, the mechanisms of TH action in the developing hippocampus are still largely unknown. In this study, we generated 3,5,3’-tri-iodo-l-thyronine (T3)-free neuronal supplement, based on the composition of neuronal supplement 21 (NS21), to examine the effect of TH in the developing hippocampus using primary cultured neurons. Effects of TH on neurons were compared between cultures in this T3-free culture medium (-T3 group) and a medium in which T3 was added (+T3 group). Morphometric analysis and RT-qPCR were performed on 7, 10, and 14 days in vitro (DIV). On 10 DIV, a decreased dendrite arborization in -T3 group was observed. Such difference was not observed on 7 and 14 DIV. Brain-derived neurotrophic factor (Bdnf) mRNA levels also decreased significantly in -T3 group on 10 DIV. We then confirmed protein levels of phosphorylated neurotrophic tyrosine kinase type 2 (NTRK2, TRKB), which is a receptor for BDNF, on 10 DIV by immunocytochemistry and Western blot analysis. Phosphorylated NTRK2 levels significantly decreased in -T3 group compared to +T3 group on 10 DIV. Considering the role of BDNF on neurodevelopment, we examined its involvement by adding BDNF on 8 and 9 DIV. Addition of 10 ng/ml BDNF recovered the suppressed dendrite arborization induced by T3 deficiency on 10 DIV. We show that the lack of TH induces a developmental delay in primary hippocampal neurons, likely caused through a decreased Bdnf expression. Thus, BDNF may play a role in TH-regulated dendritogenesis.

Neurite Outgrowth Inhibitor (NogoA) Is Upregulated in White Matter Lesions of Complex Cortical Malformations

Complex cortical malformations (CCMs), such as hemimegalencephaly and polymicrogyria, are associated with drug-resistant epilepsy and developmental impairment. They share certain neuropathological characteristics including mammalian target of rapamycin (mTOR) activation and an atypical number of white matter neurons. To get a better understanding of the pathobiology of the lesion architecture, we investigated the role of neurite outgrowth inhibitor A (NogoA), a known regulator of neuronal migration. Epilepsy surgery specimens from 16 CCM patients were analyzed and compared with sections of focal cortical dysplasia IIB (FCD IIB, n = 22), tuberous sclerosis complex (TSC, n = 8) as well as healthy controls (n = 15). Immunohistochemistry was used to characterize NogoA, myelination, and mTOR signaling. Digital slides were evaluated automatically with ImageJ. NogoA staining showed a significantly higher expression within the white matter of CCM and FCD IIB, whereas cortical tubers presented levels similar to controls. Further analysis of possible associations of NogoA with other factors revealed a positive correlation with mTOR and seizure frequency. To identify the main expressing NogoA cell type, double staining revealed dysmorphic neuronal white matter cells. Increased NogoA expression is associated with profound inhibition of neuritic sprouting and therefore contributes to a decrease in neuronal network complexity in CCM patients.

Testing the Independent and Joint Contribution of Exposure to Neurodevelopmental Adversity and Childhood Trauma to Risk of Psychotic Experiences in Adulthood

Exposure to neurodevelopmental adversity and childhood trauma are both independently associated with psychosis. However, there is little research on the mechanism underlying their relationship with each other. The current study investigated both the independent and joint effects of neurodevelopmental adversity and childhood trauma to better understand the etiology of psychosis. A large population-based cohort (N = 3514) followed from birth was assessed on psychotic experiences (PE) at 24 years. Neurodevelopmental adversity included obstetric complications (birth weight, gestational age, in-utero influenza exposure, resuscitation) and developmental impairment (cognitive and motor impairments). Trauma exposure included caregiver and peer inflicted trauma up to 17 years. Multiple regression models tested their independent and interactive effect on PE, and path analysis estimated the indirect effect of neurodevelopmental adversity on PE via trauma. Neurodevelopmental adversity (OR = 1.32, 95%CI: 1.08–1.62) and trauma (OR = 1.97, 95%CI: 1.65–2.36) independently increased the odds of PE. There was also an indirect relationship between neurodevelopmental adversity and PE via increased exposure to childhood trauma (β = 0.01, 95%CI: 0.004–0.024). In particular, peer bullying mediated the association between developmental impairment to PE (β = 0.02, 95%CI: 0.01–0.03). In conclusion, children with neurodevelopmental adversity, in particular those with developmental impairment, are more likely to be exposed to trauma. This new etiological understanding of psychosis suggests that PE may be partially modifiable through reducing exposure to peer bullying, especially in children with developmental impairment.

THE CONTENT ASPECT OF THE IMAGE “I” IN THE STRUCTURE OF TEACHERS’ PERSONAL IDENTITY AT DIFFERENT STAGES OF PROFESSIONAL DEVELOPMENT

В меняющихся социально-экономических условиях происходит нарушение развития личностной идентичности педагогов, что приводит к искажению (деформации) ее структурных компонентов. В связи с этим необходим научный поиск путей преодоления кризиса идентичности и построение программ развития подсистем личностной (индивидуальной) и социальной (профессиональной) идентичности педагогов, адекватных изменившимся условиям. В работе изучены уровни дифференцированности идентичности, рефлексивности, особенности эмоционально-оценочного тона идентификационных характеристик, соотношение личностных и социальных компонент в самоопределении идентичности. Выборку исследования составили 132 педагога образовательных учреждений г. Киселёвска Кемеровской области в возрасте 24–63 лет с педагогическим стажем от 1 года до 35 лет. Все педагоги разделены на шесть групп в соответствии с периодизацией профессионального становления В. А. Дмитриевского. Для всех испытуемых характерна негармоничность элементов идентичности, преобладание социальных компонент (учебно-профессиональные и семейно-клановые характеристики) в структуре самоописаний, средний уровень рефлексивности и низкий уровень самопринятия. Полученные данные интерпретируются с точки зрения теорий профессионального становления и формирования идентичности. In the changing socio-economic conditions there is a developmental impairment of teachers’ personal identity, which leads to a distortion (deformation) of its structural components. The relevance of the study is due to the need for a scientific search for ways to overcome the identity crisis and build programs for the development of subsystems of personal (individual) and social (professional) teachers’ identity that are adequate to changing conditions. The aim of the study was to investigate the levels of differentiation, reflexivity, features of the emotional-evaluative tone of identification characteristics, the ratio of personal and social components in self-determination of identity. Research sample consists of 132 teachers of educational institutions of the city of Kiselevsk, Kemerovo region, aged 24 to 63 years, with pedagogical experience from 1 year to 35 years. All teachers were divided into 6 groups in accordance with the periodization of the professional development of V. A. Dmitrievsky. All subjects were characterized by the the inharmony of elements of identity, the predominance of social components (educational, professional and family-clan characteristics) in the structure of self-descriptions, the average level of reflectivity and a low level of self-acceptance. The received data were interpreted from the point of view of theories of professional formation and identity formation.