Awareness of children's developmental problems and sharing of concerns with parents by preschool teachers and childcare workers: The Japanese context.

BACKGROUND: This study aims to determine the extent to which preschool teachers and childcare workers are aware of the presence of developmental problems among children and to what extent they share information with parents about their concerns regarding a child's development or diagnosis of neurodevelopmental disorders (NDDs). METHODS: We wrote to all 924 preschools and childcare centres in Japan's Nagano and Yamanashi prefectures to request participants. We then sent survey forms to the preschools and childcare centres that agreed to cooperate for three grades comprising 3-, 4- and 5-year-olds in the school year 2020. We asked the staff member in charge of each child to complete the survey. The survey included questions about the teacher's concerns regarding the possibility of an NDD and whether the matter had been shared with the children's parents. RESULTS: We obtained data for 10 354 children from 206 preschools and childcare centres (response rate = 22.3%). Among these children, 457 (4.4%) had an NDD diagnosis that their parents shared with the teachers. However, the teachers of 1274 children (12.3%) had concerns regarding their development but were not informed by the parents about the diagnosis, if any. These 1274 children included 775 (60.8%) cases where the teachers failed to share their concerns with parents because (1) the teachers could not communicate with parents (n = 119), (2) the teachers were not sure if there was a neurodevelopmental problem (n = 360) and (3) the parents were not aware of the problem (n = 296). CONCLUSIONS: Preschool teachers and childcare workers had concerns about the development of a substantial proportion of children in their charge. However, teachers and childcare workers did not share their concerns regarding many children's developmental problems with their parents. The findings suggest that there are challenges in information-sharing between teachers/childcare workers and parents.

Transmission Risk of Severe Acute Respiratory Syndrome Coronavirus 2 before and after Symptom Onset of the Infector.

An outbreak of coronavirus 2019 (COVID-19) occurred in Ueda City, Nagano prefecture, Japan, which has a population of 150,000. The residents were a population naïve to COVID-19, and many of them had only one chance of exposure, in which careful epidemiological investigation could reveal attack rates among close contact on the specific date of exposure. We identified 89 cases and 328 close contacts. Among the close contacts, 114 had only one chance of exposure to the 20 index cases. During the follow-up period, 17 close contacts tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), overall attack rate of 15%, after the exposure to 6 infectors. The median number of close contacts for the 6 infectors was 5.5 (range 2-14). Attack rates among these close contacts were 13% (1/8), 20% (2/5), 33% (2/6), 50% (1/2), 64% (4/9 and 5/5), and 100% (2/2), respectively. The transmission risk of SARS-CoV-2 appears to peak one day before symptom onset, and is at similar levels two days before (16%) and on the day (20%) of symptom onset. A multidisciplinary approach is needed to control the COVID-19 outbreak, in addition to investigation, which began after case identification.

NOTCH1 mutation in a female with myeloid/NK cell precursor acute leukemia.

A 6-year-old Japanese female was diagnosed as having myeloid/NK cell precursor acute leukemia (MNKL) using immunocytochemical analysis. The patient was treated by cord blood transplantation from an HLA 1-locus mismatched unrelated donor after chemotherapy comprising cytosine arabinoside, idarubicin, etoposide, and L-asparaginase. We detected a nonsense mutation, C7412A, resulting in S2471X, where X is a terminal codon, in the PEST domain of NOTCH1 in this patient. The presence of the NOTCH1 activating mutation in MNKL might suggest a possible role in the leukemogenesis of MNKL.

Increased serum monocyte chemoattractant protein-1, macrophage inflammatory protein-1beta, and interleukin-8 concentrations in hemophagocytic lymphohistiocytosis.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is characterized by hypercytokinemia caused by macrophage and T cell activation. We analyzed the serum concentrations of monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1beta, and interleukin (IL)-8 to investigate the roles of these chemokines in the pathophysiology of HLH. METHODS: Seven patients clinically diagnosed with HLH were examined. Serum cytokines and chemokines were measured. The differences in the serum concentrations between the patients with HLH and the controls were investigated. RESULTS: In patients with an active phase of HLH, the serum MCP-1, MIP-1beta, and IL-8 levels all were significantly higher than in healthy controls. The chemokine elevations decreased rapidly after initiation of chemotherapy. During increases in disease activity, elevation of MCP-1 and MIP-1beta preceded elevation of the serum ferritin level, which is a clinical indicator of HLH disease activity. CONCLUSIONS: These results suggest that MCP-1, MIP-1beta, and IL-8 play important roles in the pathophysiology of HLH. In addition, the serum concentrations of these chemokines may be sensitive markers for assessing disease activity in patients with HLH.

The detection and quantification of highly reactive oxygen species using the novel HPF fluorescence probe in a rat model of focal cerebral ischemia.

A novel fluorescence probe, 2-[6-(4'-hydroxy) phenoxy-3H-xanthen-3-on-9-yl] benzoic acid (HPF) was used to investigate the generation of highly reactive oxygen species (hROS) under ischemia both in vitro and in vivo. In the in vitro study, HT 22 cells were used to demonstrate that was predominantly detected in the cytoplasm, which coincides with the location of the mitochondria and then its HPF fluorescence gradually increased from 6 to 24 h due to glutamate induced oxidative stress. In the in vivo study, the permanent and transient middle cerebral artery occlusion (MCAO) was induced in rats. Brain slices were incubated in an artificial medium containing HPF. The area of enhanced HPF fluorescence existed in both the ischemic core and the peri-infarct area at 4h after MCAO in both permanent and transient MCAO models. The area extended beyond the boundary of the ischemic damage into biochemically viable tissue. The enhanced fluorescent intensity following transient MCAO was higher than that observed in the permanent MCAO model. Hydroxyl radical scavenger, MCI-186 significantly suppressed the enhanced fluorescence intensity. This study demonstrated that HPF has a high sensitivity and specificity for the detection of hROS in focal cerebral ischemia as well as in a cellular model of oxidative stress.

Effects of a novel glutamate transporter blocker, (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA), on activities of hippocampal neurons.

Glutamate transporters rapidly take up synaptically released glutamate and maintain the glutamate concentration in the synaptic cleft at a low level. (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA) is a novel glutamate transporter blocker that potently suppresses the activity of glial transporters. TFB-TBOA inhibited synaptically activated transporter currents (STCs) in astrocytes in the stratum radiatum in rat hippocampal slices in a dose-dependent manner with an IC50 of 13 nM, and reduced them to approximately 10% of the control at 100 nM. We investigated the effects of TFB-TBOA on glutamatergic synaptic transmission and cell excitability in CA1 pyramidal cells. TFB-TBOA (100 nM) prolonged the decay of N-methyl-D-aspartic acid receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs), whereas it prolonged that of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated EPSCs only when the desensitization of AMPARs was reduced by cyclothiazide (CTZ). Furthermore, long-term application of TFB-TBOA induced spontaneous epileptiform discharges with a continuous depolarization shift of membrane potential. These epileptiform activities were mainly attributed to NMDAR activation. Even after pharmacological block of NMDARs, however, TFB-TBOA induced similar changes by activating AMPARs in the presence of CTZ. Thus, the continuous uptake of synaptically released glutamate by glial transporters is indispensable for protecting hippocampal neurons from glutamate receptor-mediated hyperexcitabilities.