Pathological study of pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): effects of lowered serum zinc level on the toxicity

Introduction. We have previously reported that Asian sand dust (ASD) induced acute and chronic inflammatory changes in the lung of mice. Zinc (Zn) is reported to influence inflammation and wound healing. The purpose of the study was to assess the effects of lowered serum Zn levels on the lung toxicity induced by ASD. Material and methods. Mice that were fed diets containing normal (group 1) or low (group 2) content of Zn for 8 weeks were intratracheally instilled with 3.0 mg of ASD, followed by sacrifice at 24 hours, 2 weeks, and 1, 2 and 3 months after instillation. Paraffin sections of lung tissues were stained by hematoxylin and eosin and by immunohistochemistry to detect tumor necrosis factor (TNF) and interleukin (IL)-1β as well as inflammasome (NALP3), autophagy (LC-3) and lysosome (LAMP-1) markers. Selected samples of lung tissue were examined by electron microscopy. Results. Following histological examination of the lung, similar patterns of inflammatory changes were observed in mice with normal and low serum Zn concentrations; however, they were more prominent and persistent in mice with low serum Zn level. These changes were both purulent (acute) and pyogranulomatous (chronic) in nature. In the lung lesions of group 2 mice the changes within the cytoplasmic vacuoles of enlarged ASD-containing macrophages (Mo) were clearly visible. The macrophages expressed TNF and IL-1β, and semi-quantitative analysis revealed a larger number of TNF-positive Mo in mice with normal level of serum Zn and a larger number of IL-1β-positive Mo in mice with low level of serum Zn. Decreased positive LC-3 staining and dilated lysosomes containing ASD particles were observed in the cytoplasm of Mo in mice with low serum Zn concentration. Conclusions. These findings suggest that low serum zinc concentration may induce the modulation of cytokine expression and lysosomal malfunction by phagocytotic and/or autophagic mechanisms, and may result in interstitial pyogranulomatous inflammation in the lungs of mice treated with ASD

Inhibition of retinoid X receptor improved the morphology, localization of desmosomal proteins and paracellular permeability in three-dimensional cultures of mouse keratinocytes.

Retinoic acid (RA) plays an important role in epithelial homeostasis and influences the morphology, proliferation, differentiation and permeability of epithelial cells. Mouse keratinocytes, K38, reconstituted non-keratinized stratified epithelium in three-dimensional (3D) cultures with serum, which contains retinol (a source of RA), but the morphology was different from in vivo epithelium. The formed epithelium was thick, with loosened cell-cell contacts. Here, we investigated whether the inhibition of RA receptor (RAR)/retinoid X receptor (RXR)-mediated signaling by an RXR antagonist, HX 531, improved K38 3D cultures in terms of morphology and intercellular junctions. The epithelium formed by 0.5 μM HX531 was thin, and the intercellular space was narrowed because of the restoration of the layer-specific distribution of desmoglein (DSG)-1, DSG3 and plakoglobin (PG). Moreover, the levels of desmosomal proteins and tight junction proteins, including DSG1, DSG2, DSG3, PG, claudin (CLDN)-1 and CLDN4 increased, but the adherens junction protein, E-cadherin, did not show any change. Furthermore, CLDN1 was recruited to occludin-positive cell-cell contacts in the superficial cells and transepithelial electrical resistance was increased. Therefore, K38 3D cultures treated with 0.5 μM HX531 provides a useful in vitro model to study intercellular junctions in the non-keratinized epithelium.福岡歯科大学2021年

Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2.

The elucidation of drug resistance mechanisms is important in the development of clinical therapies for the treatment of leukemia. To study the drug resistance mechanisms, protein expression profiles of 1-β-D-arabinofuranosylcytosine (AraC)-sensitive K562 (K562S) cells and AraC-resistant K562 (K562AC) cells were compared using two-dimensional fluorescence difference gel electrophoresis. In a comparison of protein expression profiles, 2073 protein spots were found to be altered, and 15 proteins of them were remarkably altered. These proteins were identified by mass spectrometry. The most differently expressed proteins were aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and vimentin. Both proteins were verified using reverse transcriptase polymerase chain reaction and Western blot analysis. ALDH1A2 protein was found to be effective in AraC resistance. ALDH1A2 knock-down induced sensitivity to AraC treatment in K562AC cells, and ALDH1A2 overexpressed K562S cells acquired the AraC resistance. Furthermore, the findings also suggest that ALDH1A2 expression is increased after the appearance of AraC resistance in clinical cases. These results will be helpful in understanding the mechanism of AraC resistance

ザイタク デ ショウガイシャ ヲ カイゴ スル コウレイ ノ カイゴシャ ニ カカワル セイカツ カイゴ ジギョウショ ショクイン ニ オケル アドバンス ケア プランニング ニンチド ト ソノ カンレン ヨウイン オウダンテキ ケンキュウ

原著論文Original Articles目的：在宅で障がい者を介護する高齢の介護者に関わる生活介護事業所職員におけるアドバンスケアプランニング（ACP）の認知度とその関連要因を調査した。方法：2022年8～10月に無記名郵送で、生活介護事業所職員を対象として調査した。従属変数は、ACPの認知の有無、独立変数は管理者か否か、年齢、性別、資格、ACP 教育・研修の有無等とした。単変量解析でP < 0.05 の有意差であった12変数に対して、ロジスティック回帰分析を行った。結果: 調査票を486事業所1,500名の対象者に配布し、69事業所141名から回収（回答率 9.4%）した。職員全体で12.1%、施設管理者が16.1%、資格別では、介護福祉士13.6%、社会福祉士17.9%、精神保健福祉士38.5%、看護師20.0%がACPを認知していた。認知度の関連要因は「精神保健福祉士の資格」（OR 7.8）「親亡き後の不安を把握」（OR 14.9）等であった。結論: 先行研究では、ACP認知度は7%で、本研究で、やや改善していたが、まだ低い状態であり、啓発が必要である。ACPを知っている職員は、管理職・医療・福祉の有資格者で、高齢の介護者に寄り添い、親亡き後の不安を把握していた。今後は、高齢の介護者支援でACPを活用する必要がある。Introduction: In Japan, support for advanced care planning (ACP) for families, including older caregivers and people with disabilities, is important. After the death of caregivers, ongoing support for decision-making for the remaining family and the socially vulnerable with unmet needs is lacking. Welfare facility staff, the cornerstone of social networks, can play a role in promoting ACP for families. Objective: A study aimed to measure awareness of ACP by administering a survey to welfare facility employees. Methods: An anonymous survey was conducted at 486 welfare facilities from August-October 2022 through the cooperation of employees. The survey investigated factors related to awareness of ACP and ACP training for support staff. Participants included managers and persons in charge of disability welfare offices, Results: The survey was distributed to 1,500 participants. One hundred forty-one responses were obtained (9.4% response rate). Of the participants, 12.1% answered that they knew about ACP; among care workers, 13.6%, social care workers, 17.9%, mental health social workers, 38.5%, and nurses, 20.0%. Factors of ACP awareness are, e.g. qualified as a mental health social worker Odds ratio (OR) 7.8, I understand the anxiety after the death of a parent OR 14.9 Conclusion: The ACP recognition rate of the participants was 7% in 2020. Thus, recognition has slightly increased. However, the overall rate remains low and must be improved. Improving the low recognition rate, analyzing the factors, and spreading are necessary. Further, we should promote better

Accuracy Comparison of Coastal Wind Speeds between WRF Simulations Using Different Input Datasets in Japan

In order to improve the accuracy of the wind speed simulated by a mesoscale model for the wind resource assessment in coastal areas, this study evaluated the effectiveness of using the Japan Meteorological Agency (JMA)'s latest and finest (2 km x 2 km) grid point value (GPV) data, produced from the local forecast model (LFM) as input data to the mesoscale model. The evaluation was performed using wind lidar measurements at two sites located on the coasts of the Sea of Japan and Pacific Ocean. The accuracy of the LFM-GPV was first compared with that of two products from the JMA Meso Scale Model (MSM) (5 km x 5 km): MSM-GPV and mesoscale analysis (MANAL). Consequently, it was shown that LFM-GPV exhibited the most accurate wind speeds against lidar measurements. Next, dynamical downscaling simulations were performed using the weather research and forecasting model (WRF) forced by the three datasets above, and their results were compared. As compared to the GPVs, it was found that the WRF dynamical downscaling simulation using them as input can improve the accuracy of the coastal wind speeds. This was attributed to the advantage of the WRF simulation to improve the negative bias from the input data, especially for the winds blowing from the sea sectors. It was also found that even if the LFM-GPV is used as an input to the WRF simulation, it does not always reproduce more accurate wind speeds, as compared to the simulations using the other two datasets. This result is partly owing to the tendency of WRF to overestimate the wind speed over land, thus obscuring the higher accuracy of the LFM-GPV. It was also shown that the overestimation tendency cannot be improved by only changing the nudging methods or the planetary boundary layer schemes in WRF. These results indicate that it may be difficult to utilize the LFM-GPV in the WRF wind simulation, unless the overestimation tendency of WRF itself is improved first

Effects of Growth Stage on the Characterization of Enterotoxin A-Producing <i>Staphylococcus aureus</i>-Derived Membrane Vesicles

Virulence factors, such as staphylococcal enterotoxin A (SEA), are contained within membrane vesicles (MVs) in the cell membrane of Staphylococcus aureus. In this study, the effects of the growth stage on quantitative and qualitative changes in the components contained in the MVs of S. aureus SEA-producing strains were examined. Changes in the expression levels of S. aureus genes were examined at each growth stage; phenol-soluble modulin (PSM) gene reached a maximum after 8 h, and the expression of cell membrane-related genes was decreased after 6 h. Based on these gene expression patterns, MVs were prepared at 6, 17, and 24 h. The particle size of MVs did not change depending on the growth stage. MVs prepared after culture for 17 h maintained their particle size when stored at 23 °C. The amount of SEA in the culture supernatant and MVs were not correlated. Bifunctional autolysin, a protein involved in cell wall biosynthesis/degradation, was increased in MVs at 17 h. The expression pattern of inflammation-related genes in human adult low calcium high temperature (HaCaT) cells induced by MVs was different for each growth stage. The inclusion components of S. aureus-derived MVs are selective, depend on the stage of growth, and may play an important role in toxicity

Current Status and Issues of Community-based Integrated Care System in Tokushima Prefecture : Health Survey of Koyadaira District, Mima City

It is predicted that the population of Tokushima Prefecture will decrease to 550,000 by 2040, and 17 municipalities will disappear. For that reason, the community-based integrated care system (integrated care) must be further developed. The purpose of integrated care is the realization of "community development which you can continue to live as you are in the area where you are accustomed to living". To achieve this, not only medical and care, but also the utilization of new human resources and resources has been demanded. In Japan, based on the Sustainable Development Goals (SDGs), relevant laws and systems will be revised to achieve the agenda set forth by 2030, and it has been strongly suggested that it is necessary to participate the welfare area (Long-term care insurance) not only in medicine but also in dentistry. In this paper, we discuss the current situation and issues of integrated care in Tokushima Prefecture, and discuss the future state in relation to the study of the Koyadaira district in Mima City, which is an area of disappearance