The establishment of childcare practice theory and research institute of child care and education

The central purpose of this paper is to establish a childcare practice theory based on metacognitive research, with an aim to solve several issues in the childcare practices at early childcare institutions. This is necessary, as there are at present no current theoretical or practical methodologies from other fields that can substitute for those outlined in this paper. The theory is constructed through fieldwork based ethnographic examination of the childcare facility ‒including both the practices of childcares, and the actions and activities of the children themselves‒ and through later analysis of field notes. Pedagogical research, in the broadest sense, cannot be successful unless it is firmly grounded in fieldwork, and with a view that overlooks the development processes of children from birth. Clinical pedagogical research must constantly be updated, reflected upon, and refined to stay relevant. For this reason, the author believes that a dedicated research institute is required as a base for further developing and maintaining the currency of this theory

Considering play when designing a daily program for children : The importance of continuity and autonomy in establishing a ‘culture of play’ in early childhood education <Special Contribution>

Each morning, when children enter their classroom, they will take some time to investigate it before choosing their own space. If experiences within this autonomously chosen space are positive, for example, through playing together happily with their friends, they will usually choose the same location the following day (and so on into the future, establishing a pattern of continuity). Consequently, their location within the room becomes a charged site where the memories of playing and learning to work together with classmates and playthings intersect. It is of vital importance for teachers to consider how these elements of continuity and autonomy can be integrated into their daily programming, because developing a strong ‘culture of play’ will allow the children to develop quickly into productive learners with fertile imaginations

Useful meal tolerance test (MTT) for carbohydrate amount and post-prandial blood glucose

Background: Low carbohydrate diet (LCD) has been effective for type 2 diabetes mellitus (T2DM), because of less post-prandial increase of blood glucose. Case presentation: The case is 62-year-old male with T2DM, who had experience of LCD a few years ago. He developed diabetic exacerbation as HbA1c 10.7% in autumn 2021. Results: He began super-LCD with 12% of carbohydrate in calorie ratio, and recorded the pictures of detail food intake every day and 45-minunte post-prandial blood glucose for long. His HbA1c decreased to 7.1% for 9 weeks. For breakfast, carbohydrate amount varies from 19.7 g to 51.1g, and 45-min post-prandial blood glucose distribute 121mg/dL to 226mg/dL. The relationship between carbohydrate amount in breakfast and 45-min post-prandial blood glucose was investigated. As a result, significant correlation was observed between them (R2=0.46, p<0.05). Regression curve revealed y=2.5897x+73.226, in which the slope of the straight line is 2.6. Discussion and Conclusion: Obtained data may suggest that carbohydrate 1g can increase post-prandial glucose 2.6mg/dL. As to the standard fact of carbohydrate metabolism in the textbook, 3.0mg/dL glucose increase per carbohydrate 1g has been observed. Restricted carbohydrate intake would be beneficial for improving glucose variability in T2DM

Inhibition of EP2/EP4 signaling abrogates IGF-1R-mediated cancer cell growth : Involvement of protein kinase C-θ activation

Associations between growth factor receptor-mediated cell signaling and cancer cell growth have been previously characterized. Receptors for prostaglandin E2, such as EP2, and EP4, play roles in cancer growth, progression and invasion. Thus, we examined the interactions between EP2/EP4- and IGF-1R-mediated cellular signaling in human pancreatic cancer cells. Selective antagonists against EP2 and EP4 abrogated IGF-1-stimulated cell growth and suppressed MEK/ERK phosphorylation. In subsequent experiments, phospho-antibody arrays indicated increased phosphorylation levels of protein kinase C-θ (PKC-θ) at the Thr538 position following the inhibition of EP2/EP4-mediated signaling. Inhibition of PKC-θ activity impaired cell viability compared with EP2/EP4-antagonized IGF-1-stimulated cells. PKC-θ kinase MAP4K3, which plays a pivotal role in PKC-θ activation, also affected growth signaling in the presence of EP2/EP4 antagonists. Administration of EP2 and EP4 antagonists significantly inhibited the growth of an orthotopic xenograft of IGF-1-secreting pancreatic cancer cells, with increased phospho-PKC-θ and decreased phospho-ERK. Clinico-pathological analyses showed that 17.4% of surgical pancreatic cancer specimens were quadruple-positive for IGF-1R, EP2 (or EP4), MAP4K3, and PKC-θ. These results indicate a novel signaling crosstalk between EP2/EP4 and IGF-1R in cancer cells, and suggest that the MAP4K3-PKC-θ axis is central and could be exploited as a molecular target for cancer therapy

Lysophosphatidic Acid Induces Allergic Inflammation

Background: Lysophosphatidic acid (LPA), a prototypic member of a large family of lysophospholipids, has been recently shown to play a role in immune responses to respiratory diseases. The involvement of LPA in allergic airway inflammation has been reported, but the mechanism remains unclear. Object: We analyzed the biological activity of LPA in vitro and in vivo and investigated its role in allergic inflammation in mice using an LPA receptor 2 (LPA2) antagonist. Methods: We used a murine model with acute allergic inflammation, in which mice are sensitized and challenged with house dust mite, and analyzed airway hyperresponsiveness (AHR), pathological findings, Th2 cytokines, and IL-33 in bronchoalveolar lavage fluid (BALF) and lung homogenates. The effect of LPA on Th2 differentiation and cytokine production was examined in vitro using naive CD4+ T cells isolated from splenocytes. We also investigated in vivo the effects of LPA on intranasal administration in mice. Results: The LPA2 antagonist suppressed the increase of AHR, the number of total cells, and eosinophils in BALF and lung tissue. It also decreased the production of IL-13 in BALF and IL-33 and CCL2 in the lung. LPA promoted Th2 cell differentiation and IL-13 production by Th2 cells in vitro. Nasal administration of LPA significantly increased the number of total cells and IL-13 in BALF via regulating the production of IL-33 and CCL-2-derived infiltrating macrophages. Conclusion: These findings suggest that LPA plays an important role in allergic airway inflammation and that the blockade of LPA2 might have therapeutic potential for bronchial asthma

Can computed tomography differentiate adenocarcinoma in situ from minimally invasive adenocarcinoma?

Background: Given the subtle pathological signs of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), effective differentiation between the two entities is crucial. However, it is difficult to predict these conditions using preoperative computed tomography (CT) imaging. In this study, we investigated whether histological diagnosis of AIS and MIA using quantitative three-dimensional CT imaging analysis could be predicted. Methods: We retrospectively analyzed the images and histopathological findings of patients with lung cancer who were diagnosed with AIS or MIA between January 2017 and June 2018. We used Synapse Vincent (v. 4.3) (Fujifilm) software to analyze the CT attenuation values and performed a histogram analysis. Results: There were 22 patients with AIS and 22 with MIA. The ground-glass nodule (GGN) rate was significantly higher in patients with AIS (p < 0.001), whereas the solid volume (p < 0.001) and solid rate (p = 0.001) were significantly higher in those with MIA. The mean (p = 0.002) and maximum (p = 0.025) CT values were significantly higher in patients with MIA. The 25th, 50th, 75th, and 97.5th percentiles (all p < 0.05) for the CT values were significantly higher in patients with MIA. Conclusions: We demonstrated that quantitative analysis of 3D-CT imaging data using software can help distinguish AIS from MIA. These analyses are useful for guiding decision-making in the surgical management of early lung cancer, as well as subsequent follow-up

非アルコール性脂肪性肝炎における肝細胞へのα-synucleinの蓄積と病理組織学的診断における有用性

Backgrounds: Nonalcoholic steatohepatitis (NASH) is characterized by fat deposition, inflammation, and hepatocellular damage. The diagnosis of NASH is confirmed pathologically, and hepatocyte ballooning is an important finding for definite diagnosis. Recently, α-synuclein deposition in multiple organs was reported in Parkinson’s disease. Since it was reported that α synuclein is taken up by hepatocytes via connexin 32, the expression of α-synuclein in the liver in NASH is of interest. The accumulation of α-synuclein in the liver in NASH was investigated. Immunostaining for p62, ubiquitin, and α-synuclein was performed, and the usefulness of immunostaining in pathological diagnosis was examined. Methods: Liver biopsy tissue specimens from 20 patients were evaluated. Several antibodies against α-synuclein, as well as antibodies against connexin 32, p62, and ubiquitin were used for immunohistochemical analyses. Staining results were evaluated by several pathologists with varying experience, and the diagnostic accuracy of ballooning was compared. Results: Polyclonal α-synuclein antibody, not the monoclonal antibody, reacted with eosinophilic aggregates in ballooning cells. Expression of connexin 32 in degenerating cells was also demonstrated. Antibodies against p62 and ubiquitin also reacted with some of the ballooning cells. In the pathologists’ evaluations, the highest interobserver agreement was obtained with hematoxylin and eosin (H&E)-stained slides, followed by slides immunostained for p62 and α-synuclein, and there were cases with different results between H&E staining and immunostaining Conclusion: These results indicate the incorporation of degenerated α-synuclein into ballooning cells, suggesting the involvement of α-synuclein in the pathogenesis of NASH. The combination of immunostaining including polyclonal α-synuclein may contribute to improving the diagnosis of NASH

Improved Insulin Resistance and Glucose Variability by Super-Low Carbohydrate Diet

Background Diabetes mellitus (DM) has been more prevalent. American Diabetes Association (ADA) proposed the Standards of Medical Care in Diabetes-2022. For nutritional therapy, low carbohydrate diet (LCD) has been recognized for its benefits. Authors have continued diabetic research concerning LCD and meal tolerance test (MTT). Case Presentation The case is 61-year-old male with type 2 diabetes mellitus (T2DM) for years. His hemoglobin A1c (HbA1c) increased to 7.8% in autumn 2021, and further evaluation and treatment was conducted including LCD, daily check of meal and carbohydrate amount, 75 g OGTT, glucagon stimulation test (GST) and others. Results He was on super-LCD method including 12% of carbohydrate. His carbohydrate intake amount and 45-minutes post-prandial blood glucose showed significant correlation. The results of 75 g OGTT twice in May 2020 and December 2021 showed that similar pattern of glucose and insulin responses and insulinogenic index (IGI). In contrast, they showed decreased fasting immuno-reactive insulin (IRI) and Homeostasis model assessment insulin resistance (HOMA-R). For GST, C-peptide showed normal response. Discussion and Conclusion Judging from the results of MTT, OGTT, GST and IGI, he seems to show rather decreased insulin resistance by LCD associated with preserved insulin secretion ability to some degree. Further investigation would be required from pathophysiological point of view

Singlet oxygen -derived nerve growth factor exacerbates airway hyperresponsiveness in a mouse model of asthma with mixed inflammation

Background: Refractory asthma, which is caused by several factors including neutrophil infiltration is a serious complication of bronchial asthma. We previously reported that nerve growth factor (NGF) is involved in AHR. NGF-derived induction of hyperalgesia is dependent on neutrophils; however, this relationship remains unclear in respiratory disease. In this study, we examined the roles of neutrophils and NGF in refractory asthma. Methods: Using intranasal house dust mite sensitization, we established a mouse model of asthma with mixed inflammation (Mix-in). AHR, NGF production and hyperinnervation of the lungs were examined with or without different inhibitory treatments. The levels of the singlet oxygen markers, 10- and 12-(Z,E)-hydroxyoctadecadienoic acids (HODE) in the lungs, were measured by liquid chromatography-tandem mass spectrometry. An in vitro experiment was also performed to evaluate the direct effect of singlet oxygen on NGF production. Results: NGF production and hyperinnervation were higher in Mix-in mice than in conventional eosinophilic-asthmatic mice and were positively correlated with AHR. Asthmatic parameters were inhibited by NGF neutralizing Abs and myeloperoxidase (MPO) inhibition. The 10- and 12-(Z,E)-HODEs levels were increased in the lungs and were positively correlated with MPO activity and NGF production. NGF was produced by bronchial epithelial cells in vitro upon stimulation with singlet oxygen. Conclusions: Our findings suggest that neutrophil MPO-derived singlet oxygen induces increased NGF production, leading to AHR and 10- and 12-(Z,E)-HODEs production. These findings may help to develop new therapies targeting this mechanism and to establish a new biomarker for non-type 2 and refractory asthma