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Practices and Challenges of Home Care Pressure Ulcer Management ; Perception of Home-visit Nurses Who Have Completed the Specified Medical Acts Training
Get PDFPurpose of the study : This study aims to clarify practices and challenges on pressure ulcer management as perceived by home-visit nurses who have completed the specified medical acts training. Methods : We gathered 8 home-visit nurses who have completed the training in Japan. First-author conducted in-depth, semi-structured individual interviews, asking for their insights on home care pressure ulcer management. Findings : We found that the home-visit nurses conducted the following practices ; [having understandings and empathy as a health care professional who engage with client’s lives with developing/worsening pressure ulcer], [pressure ulcer care at its best within limited resources], [systematic advice and guidance to caregivers and other professionals], and [demonstration of nursing as the post-training nurse of the specified medical acts]. We also learn that the home-visit nurses were faced with following challenges : [difficulties in smoothly collaborating with multiple professionals from different organizations], [not reaching a high level of expertise or skill], [limitations under the long-term care and medical insurance systems] and [impact of COVID-19]. Conclusion : Home-visit nurses who have completed the specified medical acts training provided the nurses worked toward raising community’s awareness of the care by providing leaderships to those involved in health care teams and collaborating with other professionals.journal articl
Modulations of the mTORC2–GATA3 axis by an isorhamnetin activated endosomal–lysosomal system of the J774.1 macrophage-like cell line
No full textThe endosomal–lysosomal system represents a crucial degradation pathway for various extracellular substances, and its dysfunction is linked to cardiovascular and neurodegenerative diseases. This degradation process involves multiple steps: (1) the uptake of extracellular molecules, (2) transport of cargos to lysosomes, and (3) digestion by lysosomal enzymes. While cellular uptake and lysosomal function are reportedly regulated by the mTORC1–TFEB axis, the key regulatory signal for cargo transport remains unclear. Notably, our previous study discovered that isorhamnetin, a dietary flavonoid, enhances endosomal–lysosomal proteolysis in the J774.1 cell line independently of the mTORC1–TFEB axis. This finding suggests the involvement of another signal in the mechanism of isorhamnetin. This study analyzes the molecular mechanism of isorhamnetin using transcriptome analysis and reveals that the transcription factor GATA3 plays a critical role in enhanced endosomal–lysosomal degradation. Our data also demonstrate that mTORC2 regulates GATA3 nuclear translocation, and the mTORC2–GATA3 axis alters endosomal formation and maturation, facilitating the efficient transport of cargos to lysosomes. This study suggests that the mTORC2–GATA3 axis might be a novel target for the degradation of abnormal substances.journal articl
Study on the Extrapolability of Current Tumorgenicity Test With Mice by Comparing the Syngeneic or Allogeneic Mouse Transplantation Model
No full textThe extrapolability of the current tumorigenicity test performed by transplanting human cell product into immunodeficient (NOG) mice was investigated. For this purpose, the susceptibility to form teratomas of NOG mice was assessed by transplanting undifferentiated human-induced pluripotent stem cells (hiPSCs) as positive control cells via the liver, striatum, or tail vein and evaluating the TPD50 value (dose required to form teratomas in half of the transplanted mice). This was then compared to the TPD50 of syngeneic or allogeneic mouse models. The TPD50 of C57/BL/6(B6)-iPSC or 129/Ola(129)-embryonic stem cell (ESC) transplanted into the liver of syngeneic mice was 4.08 × 105 and 4.64 × 104 cells, respectively, while the TPD50 of hiPSC administered into the liver of NOG mice was 4.64 × 104 cells. The TPD50 of B6-miPSC-synergic, 129-mESC-synergic, or 129-cell/B6 allogeneic transplantation into the striatum was 5.09 × 102, 1.0 × 104, and 3.73 × 104 cells, respectively, while that of hiPSC/NOG mice was 1.0 × 103 cells. The TPD50 for B6-miPSC or 129-mESC syngeneic tail vein infusion was 3.16 × 106 or 5.62 × 106 cells, respectively, while no incidence was observed from 1 × 107 B6-miPSCs in 129 mice or hiPSCs in NOG mice infusion study. Although the number of data sets was limited, these data indicate that the teratoma formation from transplanted undifferentiated hiPSCs via the liver or striatum in NOG mice is comparable to that in syngeneic or allogeneic mouse transplantation model, suggesting that the result of the current tumorigenicity test in NOG mice would provide useful information to infer the incidence of teratoma from residual undifferentiated hPSCs in hPSC-derived products after transplantation.journal articl
白金化合物L3吸収端XANESホワイトライン強度評価法と酸化数 : 実験室型装置による観察
No full textPt L3 edge XANES spectra of various kinds of platinum compounds were recorded using a laboratory-type X-ray absorption spectrometer. In order to investigate precision and the accuracy for oxidation state analysis of platinum species with a simple method, the white line intensity was evaluated by least squares fitting using four kinds of profile functions (Gaussian, Lorentzian and two types of pseudo-Voigt functions) and one arctangent function for continuum state. Differences in estimated values and the deviations depending on the type of profile function adopted were discussed. White line intensity could be determined easily and reproducibly using pseudo-Voigt function where a fraction of Lorentzian function is variable. The relationship between oxidation number of Pt compounds and white line area obtained by pseudo-Voigt method are the most preferable. The height of the white line for divalent compounds varies greatly in some cases, and then it is inappropriate to apply the height to estimation of the oxidation number of unknown samples. The changes in platinum species of silica supported Pt(NH3)4Cl2 of a catalyst precursor during air calcination was examined by in-situ XANES. The platinum species exist as divalent species up to 473 K, and changed to zero-valent between 473 and 573 K. The present in-situ laboratory XAFS experiment and the oxidation state analysis is consistent with SR XAFS studies by other research group.journal articl
The effect of education regarding treatment guidelines for schizophrenia and major depressive disorders on psychiatrists' hypnotic medication prescribing behavior : a multicenter study
Get PDFBackground: To examine whether the "Effectiveness of Guideline for Dissemination and Education in psychiatric treatment (EGIUDE)" project affects the rate of prescriptions of hypnotic medication and the type of hypnotic medications prescribed among psychiatrists, for schizophrenia and major depressive disorder in Japan.
Methods: The EGUIDE project is a nationwide prospective study of evidence-based clinical guidelines for schizophrenia and major depressive disorder in Japan. From 2016 to 2021, clinical and prescribing data from patients discharged from hospitals participating in the EGUIDE project were used to examine hypnotic medication prescriptions The prescribing rate of hypnotics and the prescribing rate of each type of hypnotic (benzodiazepine receptor agonist, nonbenzodiazepine receptor agonist, melatonin receptor agonist, and orexin receptor antagonist) were compared among patients who had been prescribed medication by psychiatrists participating in the EGUIDE project and patients who had been prescribed medication by nonparticipating psychiatrists. Multivariate logistic regression analysis was performed to examine the effect of the EGUIDE project on the prescription of hypnotic medications.
Results: A total of 12,161 patients with schizophrenia and 6,167 patients with major depressive disorder were included. Psychiatrists participating in the EGUIDE project significantly reduced the rate of prescribing hypnotic medication and benzodiazepine receptor agonists for both schizophrenia (P < 0.001) and major depressive disorder (P < 0.001) patients.
Conclusion: This is the first study to investigate the educational effects of guidelines for the treatment of psychiatric disorders on psychiatrists in terms of prescribing hypnotic medications to patients. The EGUIDE project may play an important role in reducing hypnotic medication prescription rates, particularly with respect to benzodiazepine receptor agonists. The results suggest that the EGUIDE project may result in improved therapeutic behavior.journal articl
Safety and Selection Criteria of Single-joint Hybrid Assistive Limb for Upper Limb Paralysis After Stroke : A Phase I Trial
Get PDFRobotic rehabilitation is a high-intensity intervention for upper limb paralysis after a stroke. This study explored the safety and feasibility of using a single-joint hybrid assistive limb (HAL-SJ) exoskeletal device for upper limb paralysis in patients with acute stroke. In total, 11 patients with stroke (6 with moderate paralysis and 5 with severe paralysis) were enrolled between October 2021 and October 2023 in a stroke care unit. The patients underwent HAL training 3 times a week for 6 sessions. No serious adverse events related to HAL-SJ occurred, and participants demonstrated significant improvements in the Fugl-Meyer Assessment Upper Extremity (FMA-UE) and Action Research Arm Test (ARAT) (pre- vs. post-intervention; p < 0.05). The minimal clinically important difference (MCID) for FMA-UE was surpassed in 5 patients (83.3%) with moderate paralysis and 2 (40.0%) with severe paralysis. Regarding ARAT, 4 patients (66.7%) with moderate paralysis exceeded the MCID, whereas none (0.0%) with severe paralysis did. These findings suggest that HAL-SJ is both safe and feasible, particularly for individuals with moderate paralysis.journal articl
Role of stromal PD-L1 expression in colorectal liver metastasis
Get PDFBackground and Aim
The outcomes of immune checkpoint blockade for colorectal cancer (CRC) treatment are unsatisfactory. Furthermore, the efficacy of immune checkpoint blockade for liver metastasis of various cancer is poor. Here, we investigated the relationship between stromal programmed death-ligand 1 (PD-L1) expression and the prognosis of patients with colorectal cancer liver metastasis (CRLM).
Methods
The present study enrolled 84 CRLM patients who underwent surgery (R0) for CRC. Immunohistochemistry was performed to analyze stromal PD-L1 expression in CRLM.
Results
Stromal PD-L1 was expressed in 52.3% of CRLM samples, which was associated with fewer not optimally resectable metastases (p=0.04). Stromal PD-L1 also tended to associate with a lower tumor grade (p=0.08). Stromal PD-L1-positive patients had longer overall survival (p=0.003). Multivariate analysis identified stromal PD-L1 expression (p=0.008) and poorer differentiation (p<0.001) as independent prognostic indicators. Furthermore, stromal PD-L1 expression was correlated to a high number of tumor-infiltrating lymphocytes (TILs). Stromal PD-L1– and low TIL groups had shorter OS than stromal PD-L1+and high TIL groups (46.6% vs. 81.8%, p=0.05) Stromal PD-L1-positive patients had longer disease-free survival (DFS) (p=0.03) and time to surgical failure (p=0.001). Interestingly, stromal PD-L1 expression was positively related to the desmoplastic subtype (p=0.0002) and inversely related to the replacement subtype of the histological growth pattern (p=0.008).
Conclusions
Stromal PD-L1 expression may be a significant prognostic marker for CRLM.journal articl
YIPF3 and YIPF4 regulate autophagic turnover of the Golgi apparatus
Get PDFThe degradation of organelles by autophagy is essential for cellular homeostasis. The Golgi apparatus has recently been demonstrated to be degraded by autophagy, but little is known about how the Golgi is recognized by the forming autophagosome. Using quantitative proteomic analysis and two novel Golgiphagy reporter systems, we found that the five-pass transmembrane Golgi-resident proteins YIPF3 and YIPF4 constitute a Golgiphagy receptor. The interaction of this complex with LC3B, GABARAP, and GABARAPL1 is dependent on a LIR motif within YIPF3 and putative phosphorylation sites immediately upstream; the stability of the complex is governed by YIPF4. Expression of a YIPF3 protein containing a mutated LIR motif caused an elongated Golgi morphology, indicating the importance of Golgi turnover via selective autophagy. The reporter assays reported here may be readily adapted to different experimental contexts to help deepen our understanding of Golgiphagy.journal articl
Asciminib, a novel allosteric inhibitor of BCR-ABL1, shows synergistic effects when used in combination with imatinib with or without drug resistance
Get PDFIn the treatment of chronic myeloid leukemia (CML), resistance to BCR-ABL inhibitors makes it difficult to continue treatment and is directly related to life expectancy. Therefore, asciminib was introduced to the market as a useful drug for overcoming drug resistance. While combining molecular targeted drugs is useful to avoid drug resistance, the new BCR-ABL inhibitor asciminib and conventional BCR-ABL inhibitors should be used as monotherapy in principle. Therefore, we investigated the synergistic effect and mechanism of the combination of asciminib and imatinib. We generated imatinib-resistant cells using the human CML cell line K562, examined the effects of imatinib and asciminib exposure on cell survival using the WST-8 assay, and comprehensively analyzed genetic variation related to drug resistance using RNA-seq and real-time PCR. A synergistic effect was observed when imatinib and asciminib were combined with or without imatinib resistance. Three genes, GRRP1, ESPN, and NOXA1, were extracted as the sites of action of asciminib. Asciminib in combination with BCR-ABL inhibitors may improve the therapeutic efficacy of conventional BCR-ABL inhibitors and prevent the development of resistance. Its dosage may be effective even at minimal doses that do not cause side effects. Further verification of this mechanism of action is needed. Additionally, cross-resistance between BCR-ABL inhibitors and asciminib may occur, which needs to be clarified through further validation as soon as possible.doctoral thesi
