Intrauterine twin environment and genetic factors subliminally affecting general movements in preterm infants.

BACKGROUND: Understanding background factors is beneficial for interpreting general movements (GMs). This study examines the factors involved in preterm-writhing GMs by comparing twins and singletons. METHOD: The subjects were 107 infants cared for at Oita University. The cohort consisted of very-low-birth-weight infants, including twins with a birth weight < 2000 g. The median gestational age (GA) was 29 weeks 1 day. The subjects consisted of 75 singletons, 32 twins (16 pairs), 20 monochorionic twins (M-twins), and 12 dichorionic twins (D-twins). GMs were scored according to the GMs optimality score (GMOS) and integrated into 6 items: the quality, neck-trunk and space, amplitude-speed, rotation, onset-offset and cramped, and tremulous score at 32-34 weeks, 35-36 weeks, and 37-42 weeks' GA. A hierarchical cluster analysis was performed using integrated GMOS, and the characteristics of clusters were examined according to clinical backgrounds. RESULTS: Three clusters were identified. Cluster 1 was characterized by good-quality GMs, cluster 2 by a poor repertoire but optimal space and rotatory components, and cluster 3 by overall poor-quality GMs, respectively. The mean GMOSs were 36.6, 31.8 and 24.3 in clusters 1, 2, and 3, respectively. There were no marked differences in proportions within clusters with respect to sex and twins. Small-for-gestational age (SGA) was significantly more frequent in cluster 3 at 32-34 weeks' GA than in other clusters. Perinatal brain injury had a significantly lower proportion in cluster 1 and a higher proportion in cluster 3 at 35-36 weeks' GA and 37-42 weeks' GA. M-twin pairs tended to belong to the same clusters at 35-36 weeks' GA. CONCLUSION: Preterm writhing GMs are associated with SGA and perinatal brain injury. Cluster matching in M-twins suggests that certain genetic factors may substantially influence GMs.

Contact-Killing Antibacterial Polystyrene Polymerized Using a Quaternized Cationic Initiator.

Contact-killing antibacterial materials are attracting attention owing to their ability for sustained antibacterial activity. However, contact-killing antibacterial polystyrene (PS) has not been extensively studied because its chemically stable structure impedes chemical modification. In this study, we developed an antibacterial PS sheet with a contact-killing surface using PS synthesized from 2,2'-azobis-[2-(1,3-dimethyl-4,5-dihydro-1H-imidazol-3-ium-2-yl)]propane triflate (ADIP) as a radical initiator with cationic moieties. The PS sheet synthesized with ADIP (ADIP-PS) exhibited antibacterial activity in contrast to PS synthesized with other azo radical initiators. Surface ζ-potential measurements revealed that only ADIP-PS had a cationic surface, which contributed to its contact-killing antibacterial activity. The ADIP-PS sheets also exhibited antibacterial activity after washing. In contrast, PS sheets containing silver, a typical leachable antibacterial agent, lost all antibacterial activity after the same washing treatment. The antibacterial ADIP-PS sheet demonstrated strong broad-spectrum activity against both Gram-positive and Gram-negative bacteria, including drug-resistant bacteria. Cytotoxicity tests using L929 cells showed that the ADIP-PS sheets were noncytotoxic. This contact-killing antibacterial PS synthesized with ADIP thus demonstrated good prospects as an easily producible antimicrobial material.

Onasemnogene Abeparvovec Treatment after Nusinersen in an Infant with Spinal Muscular Atrophy Type 1.

BACKGROUND: Until recently, the treatment of spinal muscular atrophy (SMA) was limited to symptomatic treatment with no cure. Three innovative drugs, nusinersen, onasemnogene abeparvovec (OA), and risdiplam have been developed to treat SMA. Although the clinical trials for these drugs have demonstrated their efficacy, there is limited information on real world treatment strategies. In this study, we present a case of a male infant with SMA type 1 who underwent OA treatment after nusinersen treatment. CASE PRESENTATION: At 4 months of age, the patient was diagnosed with SMA type 1. At 6 months of age, nusinersen treatment was initiated. His motor function improved, but the effect was limited; therefore, his parents requested gene replacement therapy. During the preparation for OA treatment, anti-adeno-associated virus 9 (AAV9) antibody tests repeatedly showed non-specific reactions, which delayed initiation of treatment. The patient was put on ventilator management after he caught a common cold. During this management, the anti-AAV9 antibody test results were negative. Furthermore, the patient showed increased transaminase levels just before OA treatment; however, since these gradually decreased without signs of liver failure, we started OA treatment at 13 months of age. Four months later, the patient began to sit without support and was weaned from non-invasive positive pressure ventilation, although nasogastric tube feeding remained partially necessary. CONCLUSION: We believe that the management of unstable SMA type 1 symptoms, anti-AAV9 antibody testing, and changes in transaminase levels will be helpful for other patients with SMA who require treatment.

Clinical characteristics of preterm and term infants with Ureaplasma in gastric fluid.

BACKGROUND: Ureaplasma spp. is an endemic microorganism that causes placental chorioamnionitis or preterm delivery in pregnant women, and the occurrence of bronchopulmonary dysplasia or intraventricular hemorrhaging in preterm infants after birth, although the pathogenicity of Ureaplasma remains controversial. The association between Ureaplasma exposure and the symptoms or outcomes of infected mothers or their infants born at term remains poorly understood. We investigated the clinical characteristics of preterm and term infants with or without Ureaplasma in their gastric fluid. METHODS: Gastric fluid samples were collected from 47 newborns in the neonatal intensive-care unit immediately after birth and tested using multiplex polymerase chain reaction (PCR) assays targeting Ureaplasma spp., Ureaplasma parvum, and Ureaplasma urealyticum. The clinical findings and outcomes of the neonates and their mothers were retrospectively evaluated. RESULTS: Ureaplasma spp. were detected in 9/47 samples (19%) by multiplex PCR assays. In all cases, the subspecies was U. parvum. The Ureaplasma-positive group had a significantly higher incidence of chorioamnionitis in utero than the Ureaplasma-negative group. Regarding preterm infants, the IgM levels in the Ureaplasma-positive group were significantly higher than in the Ureaplasma-negative group. In contrast, in term infants, the rates of a non-reassuring fetal status, a maternal fever, and maternal leukocyte counts and maternal C-reactive protein levels within five days before delivery in the Ureaplasma-positive group were significantly higher than those in the Ureaplasma-negative group. All three extremely-low-birth-weight infants with Ureaplasma developed bronchopulmonary dysplasia. The length of hospitalization in the Ureaplasma-positive group was almost same as that in the Ureaplasma-negative group for term infants. CONCLUSION: Mothers or their fetuses with exposure to Ureaplasma expressed characteristic clinical features during pregnancy and after birth.

Early infantile spontaneous movement in very low birthweight infants is associated with sensory characteristics at the corrected age of 3 years.

AIM: To clarify the relationship between early infantile spontaneous movement of very-low-birth-weight infants (VLBWIs) and sensory characteristics in childhood. STUDY DESIGN: Prospective cohort study. We investigated the association between the Motor Optimality Score-Revised (MOS-R), a detailed assessment of general movements (GMs) at the corrected age of 9-17 weeks and the Infant/Toddler Sensory Profile Japanese version (ITSP-J) at the corrected age of 3 years. A multiple regression analysis was performed to examine the correlation of ITSP-J and MOS-R with patient clinical background factors. SUBJECTS: Fifty-three VLBWIs (median gestational age: 28 weeks, 6 days; median birth weight: 997 g) who were managed at the NICU of Oita University from September 2013 to June 2019. RESULTS: A multiple regression analysis revealed that the ITSP-J subscale in the sensory section of visual score was significantly correlated with the age-adequate movement repertoire subscore of MOS-R, and in the sensory section of vestibular score was correlated with the fidgety subscore of MOS-R. For both visual and vestibular section scores, intraventricular hemorrhage (IVH) showed an independent association with the MOS-R subscore. CONCLUSION: Spontaneous movement characteristics in early infancy were associated with sensory characteristics in early childhood.

Immune-Triggered Forms of Plasticity Across Brain Regions.

Immune cells play numerous roles in the host defense against the invasion of microorganisms and pathogens, which induces the release of inflammatory mediators (e.g., cytokines and chemokines). In the CNS, microglia is the major resident immune cell. Recent efforts have revealed the diversity of the cell types and the heterogeneity of their functions. The refinement of the synapse structure was a hallmark feature of the microglia, while they are also involved in the myelination and capillary dynamics. Another promising feature is the modulation of the synaptic transmission as synaptic plasticity and the intrinsic excitability of neurons as non-synaptic plasticity. Those modulations of physiological properties of neurons are considered induced by both transient and chronic exposures to inflammatory mediators, which cause behavioral disorders seen in mental illness. It is plausible for astrocytes and pericytes other than microglia and macrophage to induce the immune-triggered plasticity of neurons. However, current understanding has yet achieved to unveil what inflammatory mediators from what immune cells or glia induce a form of plasticity modulating pre-, post-synaptic functions and intrinsic excitability of neurons. It is still unclear what ion channels and intracellular signaling of what types of neurons in which brain regions of the CNS are involved. In this review, we introduce the ubiquitous modulation of the synaptic efficacy and the intrinsic excitability across the brain by immune cells and related inflammatory cytokines with the mechanism for induction. Specifically, we compare neuro-modulation mechanisms by microglia of the intrinsic excitability of cerebellar Purkinje neurons with cerebral pyramidal neurons, stressing the inverted directionality of the plasticity. We also discuss the suppression and augmentation of the extent of plasticity by inflammatory mediators, as the meta-plasticity by immunity. Lastly, we sum up forms of immune-triggered plasticity in the different brain regions with disease relevance. Together, brain immunity influences our cognition, sense, memory, and behavior via immune-triggered plasticity.

Secular Trends in Obesity and Serum Lipid Values among Children in Oita City, Japan, during a 27-Year Period.

AIMS: We assessed 27-year trends in obesity and blood lipid levels of 10-year-old children to estimate the risk of metabolic syndrome in adulthood. METHODS: Based on a screening program for lifestyle-related diseases in school children in Oita City, Japan, we evaluated secular trends in height, weight, percentage of overweight (POW), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), and non-HDL cholesterol (non-HDL-C) of fifth graders (median age: 10.8 years) in Oita City from 1991 to 2017. We focused on the secular trend in the percentage of children with inappropriate serum levels of each lipid. We also evaluated the long-term trends in the 95th, 50th, and 5th percentiles for each parameter, as dependent variables, with the calendar year as an independent variable. Percentages of children with mild obesity (POW-20), moderate obesity (POW-30), and severe obesity (POW-50) were set as dependent variables. RESULTS: A total of 58,699 boys and 56,864 girls were evaluated during the study period. The percentage of children with severe obesity (POW-50) consistently increased during these years, and the 95th percentile of degree of obesity significantly increased in both boys and girls. The plot of percentages of children with inappropriate levels of TC, TG, and non-HDL-C showed a mild inverted U shape during the study period. The HDL-C level typically decreased in the study period, and the TC, TG, and non-HDL-C levels were markedly higher while the HDL level was lower in obese children than in non-obese children. CONCLUSION: The number of children with severe obesity increased, and obese children had higher percentages of inappropriate lipid levels than non-obese children. The rate of dyslipidemia with low HDL levels gradually increased in all children in Oita City, Japan, over the past 27 years.

The autophagy reaction in the human umbilical cord: a potential marker for estimating fetal nutrition and neonatal growth.

OBJECTIVE: To assess the induction of autophagy in the human umbilical cord for physiological adaptation against starvation. METHODS: The expression of autophagy-related proteins (LC3-II, p62) in umbilical cord tissues from 40 neonates was assessed by Western blotting. The correlation between the expression of autophagy-related proteins and maternal findings (height, weight, body mass index [BMI]), placental weight, neonatal findings (gestational age, height, weight, Apgar score at 1 min and 5 min), and the pH of the umbilical arterial blood were analyzed using Spearman's rank correlation coefficient test (p values of <.05 were considered significant). Venous blood findings (pH, pCO2, glucose, total protein, albumin, and lactic acid) were also evaluated in 16 neonates admitted to the NICU. RESULTS: The expression of LC3-II was positively correlated with serum total protein (ρ = 0.564, p = .023). The p62 level was also correlated with maternal BMI (ρ = 0.376, p = .017), the neonatal Apgar score at 1 min (ρ = 0.331 p = .037), total protein (ρ = 0.588, p = .017), and albumin (ρ = 0.552, p = .027) positively. A multiple linear regression analysis that included clinical parameters related to fetal nutrition and neonatal growth revealed that serum total protein was significantly associated with both LC3-II (p = .024) and p62 (p = .034) in the umbilical cord. CONCLUSION: The LC3-II or p62 expression in the umbilical cord may suggest the autophagy reaction for the homeostasis of protein or amino acid metabolism in the perinatal period.

An autopsy case of recurrent pneumothorax and peliosis-like intrapulmonary hematoma with X-linked myotubular myopathy.

BACKGROUND: The typical non-muscle complications of long-surviving X-linked myotubular myopathy (XLMTM) include scoliosis, head deformity, macrocephaly, gastroesophageal reflux disease and peliosis hepatis. Recently, pulmonary blebs and recurrent pneumothorax have also been reported as uncommon complications, whereas no reports on autopsy cases have focused on lung lesions. CASE PRESENTATION: An 8-year-old boy with XLMTM presented recurrent pneumothorax requiring bleb resection and pleurodesis. He subsequently developed multiple pulmonary mass lesions. He died of hemorrhagic shock due to peliosis hepatis. Autopsy showed multiple peliosis-like hematomas in the blebs of the lung. The histopathological examination of the hematomas revealed pooled blood without a pathway to bronchus. No apparent increase in desmin- or α-smooth muscle actin (α-SMA)-positive cells, namely myofibroblasts, was observed around hematomas, suggesting that the mutation in the myotubularin gene was involved in the defective repair process in the liver and lung tissues. CONCLUSION: Recurrent pneumothorax should be considered as a non-muscle complication of XLMTM. Peliosis-like intrapulmonary hematoma may also be a critical complication caused by poor proliferation of myofibroblasts in the tissue repair process.

Vitellogenin-derived fragment in embryos of Japanese flounder Paralichthys olivaceus with binding and bactericidal activities against an infectious bacterium via an interaction with saccharides.

Thirty- and 90-kDa proteins with binding ability to Edwardsiella tarda, a causative bacterium of Edwardsiellosis in fish, were purified from the embryo of Japanese flounder Paralichthys olivaceus. The proteins were isolated with affinity chromatography, in which the bacterium was used as a ligand and galactose, mannose, and ethylenediaminetetraacetic acid (EDTA) were used as elution agents, followed by gel filtration chromatography. N-terminal amino acid sequencing and liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (LC/Q-TOF-MS) analysis revealed that the 90-kDa protein was lipovitellin heavy-chain (LvH), which is one of the proteolytically cleaved products of maternal vitellogenin (Vg) and represents the main precursor of the egg yolk in teleosts, and the 30-kDa protein was an N-terminal bit of LvH. On the other hand, Vg in the serum of the mother fish did not bind to E. tarda. While the 90-kDa protein did not show anti-bacterial activity, the 30-kDa protein strongly exhibited activity toward E. tarda, with a minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) below 0.06 µM, suggesting that the latter protein plays an important role during embryogenesis in the flounder. This is the first report showing that Vg-derived products have monosaccharides-binding activity and a fragment derived from LvH exhibits bactericidal activity.

An Algorithm for the Detection of General Movements of Preterm Infants Based on the Instantaneous Heart Rate.

Video recording and editing of general movements (GMs) takes time. We devised an algorithm to automatically extract the period of GMs emergence to assist in the assessment of GMs. The algorithm consisted of δHR: subtracting the moving average heart rate (HR) for the past 60 s from the average instantaneous HR; and %δHR: the percentage of the instantaneous HR to the moving average HR. Ten-second sections in which δHR was positive for three consecutive sections and contained at least one section with %δHR > 105% were extracted. Extracted periods are called automated extraction sections (AESs). We evaluated the concordance rate between AESs and GMs in three periods (gestational age 24−32, 33−34, and 35−36 weeks). The records of 84 very low birth weight infants were evaluated. Approximately 90% of AESs were accompanied by GMs at any period in both the supine and prone positions. The proportion of full-course (beginning to end) GMs among GMs in the AES was 80−85% in the supine position and 90% in the prone position in all periods. We could extract a sufficient number of assessable GMs with this algorithm, which is expected to be widely used for assisting in the assessment of GMs.

Fidgety Movements Assessment Accuracy Survey in Japan.

To investigate the accuracy of fidgety movements (FMs) assessment in Japanese assessors. Sixty specialists participated in the first survey. Of the participants, 18 were assessors certified by the GMs basic-training course. The surveys were composed of FMs assessment of 20 video clips. The correct assessment rates (CARs) were investigated. The survey videos were judged into three types: normal (F + +, F +), abnormal (AF) and absent (F + -, F -). After the first survey, each participant performed a self-learning exercise using clips of the first survey. The follow-up survey was conducted three months after the first survey. The median CAR of the first survey was 65% in certified assessors and 50% in noncertified assessors. The median CARs of certified assessors were significantly higher than that of noncertified assessors for all clips and for normal FMs and AF clips (p < 0.01). After 3 months of self-learning exercise the CARs in each judgement type improved in 28 follow-up survey participants. Their median CAR improved from 60% in the first survey to 84% in the follow-up survey. To practise general movements assessment (GMA), course certification is required. The self-learning exercise with the confirmed judgement FMs clips may be effective for improving the ability of FMs judgement.

Unilateral Sensorineural Hearing Loss in Children Associated With Sjögren's Syndrome.

The occurrence of unilateral sensorineural hearing loss (SNHL) during school age is relatively rare and accounts for approximately 6% of all deafness in childhood. We present two cases involving children who were diagnosed with SNHL associated with Sjögren's syndrome (SS). Case 1: An eight-year-old girl with an approximately two-year clinical history of gradual hearing loss was diagnosed with SNHL associated with SS based on histological findings of inflammation in the salivary glands and the presence of serum anti-Sjögren's syndrome-A antibody. Case 2: An eight-year-old boy with acute idiopathic thrombocytopenic purpura in whom unilateral hearing loss, which was not associated with any problems in daily life, was detected during hospitalization and who was finally diagnosed with SNHL and SS. Steroid treatment was ineffective for both patients. The previously unrecognized combination of SNHL with SS should be considered in the diagnosis of unilateral SNHL, even in children.

Mechanical Property of Polypropylene Gels Associated with That of Molten Polypropylenes.

This study aims to understand the fundamental mechanical relationship between polypropylene (PP)-gels and solid PPs without solvent through mechanical and thermal analyses, by which the mechanical similarities between molten PPs and PP gels were found, leading to the reliable estimate of the mechanical properties of semi-crystalline gels. The gelation of syndiotactic and isotactic polypropylenes (sPP and iPP) was found when PPs were dissolved in 1,2,3,4-tetrahydronaphthalene (tetralin). Interestingly, it was found that the storage modulus of sPP-gel became higher than that of iPP-gel at low PP concentration (<~40 wt%). The result was distinctly different from the result of neat solid PPs (without solvent), where the modulus of solid sPP is generally significantly lower than that of solid iPP. Such inversion behavior in the mechanical property of semi-crystalline gels had not been reported and discussed before. By further investigation of the storage moduli of neat sPP and iPP, it was found that the storage modulus of sPP became higher than that of iPP above the melting points of PP, which was similar to the behavior of the storage moduli observed in the diluted PP-gels. Such similarity between PP-gels and PP melts was also observed within iPP samples with different molecular weights.

Isolation and characterization of hirame aquareovirus (HAqRV): A new Aquareovirus isolated from diseased hirame Paralichthys olivaceus.

We isolated a novel Aquareovirus (hirame aquareovirus: HAqRV) from Japanese flounder Paralichthys olivaceus suffering from reovirus-like infection. In electron microscopy, the spherical virion (75 nm in diameter) was observed with multi-layered capsid structure. The viral genome consisted of 11 segments and regions encoding 7 virion structural proteins and 5 non-structural proteins were predicted. The deduced amino acid sequences of those proteins were highly similar to those of the aquareoviruses. However, the similarity of complete genome sequence between the HAqRV and other aquareoviruses was less than 60%. Phylogenetic analyses based on the deduced amino acid sequences suggested that the HAqRV is not classified into the known species of Aquareovirus. Pathogenicity of HAqRV was clearly demonstrated in accordance with Koch's postulates by experimental infection using Japanese flounder. The results suggest that the HAqRV is a new Aquareovirus species which is highly virulent for the Japanese flounder at early life stages.

X-linked mental retardation and severe short stature with a novel mutation of the KDM5C gene.

Many monogenetic disorders of short stature have autosomal recessive/dominant form of inheritance. However, X-linked short stature has not been well recognized. Herein, we report a case of a boy from a family with familial severe short stature and mental retardation, who displayed an X-linked recessive trait. The boy at the age of 4 yr and 6 mo presented with remarkable growth failure (height: 76.5 cm [-6.3 SD]) and mental retardation (IQ: 30) and cerebellar volume loss and without an external anomaly or microcephaly to our hospital. A careful interview to determine the family history suggested a genetic background of familial mental retardation and short stature. His mother had mild intellectual disability with normal stature and his maternal uncle had severe mental retardation with remarkably short stature. Whole-exome sequencing identified a pathogenic variant in the KDM5C gene, NM_004187: exon 23: c.3874_3875del: (p.Ala1292Glnfs*7). He presented with a novel frameshift mutation. His mother was a heterozygous carrier of the variant. This case suggests that a disorder associated with the KDM5C gene should be considered when patients present with remarkably short stature and X-linked mental retardation.