Development of an In Vitro Assessment Method for Chemotherapy-Induced Peripheral Neuropathy (CIPN) by Integrating a Microphysiological System (MPS) with Morphological Deep Learning of Soma and Axonal Images.

Several anticancer drugs used in cancer therapy induce chemotherapy-induced peripheral neuropathy (CIPN), leading to dose reduction or therapy cessation. Consequently, there is a demand for an in vitro assessment method to predict CIPN and mechanisms of action (MoA) in drug candidate compounds. In this study, a method assessing the toxic effects of anticancer drugs on soma and axons using deep learning image analysis is developed, culturing primary rat dorsal root ganglion neurons with a microphysiological system (MPS) that separates soma from neural processes and training two artificial intelligence (AI) models on soma and axonal area images. Exposing the control compound DMSO, negative compound sucrose, and known CIPN-causing drugs (paclitaxel, vincristine, oxaliplatin, suramin, bortezomib) for 24 h, results show the somatic area-learning AI detected significant cytotoxicity for paclitaxel (* p < 0.05) and oxaliplatin (* p < 0.05). In addition, axonal area-learning AI detected significant axonopathy with paclitaxel (* p < 0.05) and vincristine (* p < 0.05). Combining these models, we detected significant toxicity in all CIPN-causing drugs (** p < 0.01) and could classify anticancer drugs based on their different MoA on neurons, suggesting that the combination of MPS-based culture segregating soma and axonal areas and AI image analysis of each area provides an effective evaluation method to predict CIPN from low concentrations and infer the MoA.

How has the COVID-19 pandemic influenced nursing students' academic experience and career choices? A qualitative descriptive analysis.

COVID-19 control measures influenced education and training environments and profoundly impacted nursing students' career prospects and academic lives. This study intends to elucidate the impact of the COVID-19 pandemic on nursing students' academic experience and career choices. A qualitative descriptive study was conducted at a 4-year university in Japan, using semi-structured interviews with 14 nursing students. Sandelowski's qualitative descriptive analysis was conducted. We identified 11 categories that summarize COVID-19's influence on students' academic experience and career choices: "Forced change to a new learning system," "Difficult learning thoroughly with restricted face-to-face interactions," "Worries regarding teacher evaluations when face-to-face interactions are restricted," "Adapting to changes in the learning environment," "Finding new ways to learn due to the different learning environment," "Worries regarding career decision-making after losing opportunities to obtain career information," "Fully utilizing limited information resources in deciding where to work while being influenced by others," "Coping with a confusing new job hunting system," "Worries about becoming a nurse without enough practical experience," "Conscious of working as a nurse while facing infections," and "Support from those around me is helpful in an unfamiliar environment." The categories comprised four elements: academic impact, employment/career impact, future impact on working as a nurse, and environmental support. Building an online education/training program, ensuring the availability of regular psychological support, providing abundant information on employment, installing an information desk, and providing regular feedback were considered imperative for supporting nursing students.

Impact of the COVID-19 pandemic on the mental health of nursing students in Japan: a cross-sectional study.

BACKGROUND: The effect of the prolonged coronavirus disease (COVID-19) pandemic on the mental health of nursing students is unclear. This study assesses the prevalence of anxiety, depression, and insomnia among nursing students in Japan during the pandemic and determines the risk factors associated with such symptoms. METHODS: An online survey-based cross-sectional study was conducted from August 16 to October 16, 2021. Participants were first- to fourth-year nursing students enrolled in undergraduate programs at the eight universities in Japan. Anxiety, depression, and insomnia were assessed using the Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Insomnia Severity Index-7, respectively. We calculated descriptive statistics for each measurement item and performed univariate and logistic regression analyses to evaluate the potential risk factors. RESULTS: We received responses from 1,222 of 3,056 nursing students (response rate: 40.0%). After 25 participants were excluded due to missing outcome values, 1,197 students (valid response rate: 98.0%) were included in the analysis. The prevalence of anxiety, depression, and insomnia was 4.8%, 12.4%, and 18.0%, respectively. The risk of anxiety was lower among participants who did not have any relatives or friends who had been infected with SARS-CoV-2 than among those who did (aOR 0.36, 95% CI 0.14-0.94). The risk of depression was higher among participants whose financial status had worsened during the pandemic than among those whose financial status had not changed (aOR 3.44; 95% CI 1.98-5.96). Common factors that increased the risk of anxiety, depression, and insomnia were life satisfaction and fear of COVID-19. CONCLUSION: Mental health-related symptoms among nursing students in Japan have not necessarily worsened with the spread of COVID-19 but were exacerbated by the intensity of changes in daily living and fear, which are psychosocial effects associated with the pandemic.

Impact of the COVID-19 pandemic on mental health of nursing students in Japan: protocol for a cross-sectional study.

INTRODUCTION: The COVID-19 pandemic is spreading globally with a high risk of mortality. It is also significantly affecting mental health. For nursing students, the impact of COVID-19 on mental health is predicted to be significant; however, sufficient data have not been obtained. Therefore, this study will aim to assess the mental health of nursing students and evaluate the related factors. METHODS AND ANALYSIS: This proposed study is a cross-sectional survey using a self-report questionnaire. An online questionnaire will be distributed among all nursing students of eight universities in Japan. The survey questionnaire will consist of questions related to demography, life satisfaction, fear of COVID-19, mental health and physical activities. The target sample size is 1300 nursing students. We will calculate descriptive statistics for each measurement item and perform univariate and logistic regression analyses to evaluate the potential risk factors for anxiety, depression and insomnia symptoms in nursing students. The strength of association will be assessed using the OR and its 95% CIs. Statistical significance will be set at a p<0.05. ETHICS AND DISSEMINATION: The protocol was approved by the Institutional Review Board (IRB) of the University of Hyogo on 22 March 2021 (ID: 2020F29). In addition, all of the participating facilities required ethical approval from their local IRBs. The findings will be disseminated through peer-reviewed publications and conference presentations. We believe that the proposed large-scale investigation of the mental health of nursing students during the COVID-19 pandemic and the relationship between mental health and fear of COVID-19 are novel and will be a strength of this study.

Cyclo olefin polymer-based solvent-free mass-productive microphysiological systems.

A microphysiological system (MPS) holds great promise for drug screening and toxicological testing as an alternative to animal models. However, this platform faces several challenges in terms of the materials used (e.g. polydimethylsiloxane; PDMS). For instance, absorption of drug candidates and fluorescent dyes into PDMS, as well as the effect elicited by materials on cultured cells, can cause inaccurate or misleading results in cell assays. The use of PDMS also poses challenges for mass production and long-term storage of fabricated MPSs. Hence, to circumvent these issues, herein we describe the development of a cyclo olefin polymer (COP)-based MPS using photobonding processes and vacuum ultraviolet (VUV), designated as COP-VUV-MPS. COP is an amorphous polymer with chemical/physical stability, high purity and optical clarity. Due to the thermostability and high modulus of COP, the metal molding processes was applied for mass production of MPSs without deformation of microstructures and with quick fabrication cycle time (approx. 10 min/cycle). Moreover, VUV photobonding process with an excimer light at a 172nm wavelength allowed assembling COP materials without the use of additional solvents and tapes, which might cause cell damages. In comparison with the conventional MPS made of PDMS (PDMS-MPS), COP-VUV-MPS showed improved chemical resistance without causing molecule absorption. Moreover, COP-VUV-MPS maintained the stemness of environmentally sensitive human-induced pluripotent stem cells without causing undesired cellular phenotypes or gene expression. These results suggest that COP-VUV-MPS may be broadly applicable for the advancement of MPS and applications in drug development, as well asin vitrotoxicological testing.

Folding and Assembly of Vanilloid Receptor Secondary-Structure Peptide with Hexahistidine Linker at Nickel-Nitrilotriacetic Acid Monolayer for Capsaicin Recognition.

Herein, we report the self-assembly of a synthetic vanilloid receptor (VR) peptide that selectively binds capsaicin. We synthesized a 26-mer peptide-YSEILFFVQS-HHHHHH-LAMGWTNMLY (S3HS4)-comprising two chemoreceptor domains of transient receptor potential channel (TRPV1) linked by a hexahistidine sequence. High-speed atomic force microscopy (AFM) imaging in water revealed that the peptide structures alternated rapidly between wedge shape and linear forms. Circular dichroism spectroscopy showed that 65% of the amide units in the peptide chain adopted an α-helix structure, which was ascribed to the chemoreceptor domains. S3HS4 developed well-packed monolayers at the Ni-treated thiolated nitrilotriacetic acid self-assembled monolayers by chelation of the hexahistidine segment, as characterized by infrared spectroscopy and AFM, which exhibited statistically constant specific height. Therefore, S3HS4 was expected to fold spontaneously upon chelation, and the resulting helix-turn-helix conformers developed films while uniformly oriented: the tilt angle was 69° from the surface normal to the substrate. According to microgravimetric analysis using a quartz crystal microbalance (QCM), the adsorption was 84 ± 47 pmol cm-2 ( n = 3), which was almost consistent with the saturation adsorption of an α-helix unit. We also used a QCM to investigate the host-guest reactions of S3HS4 and found that the S3HS4-attached QCM-chip-bound capsaicin with an apparent binding constant of (4.2 ± 3.6) × 104 M-1 ( n = 4), whereas there was no evidence of binding to vanillin or acetophenone. Two controls-a blank chip without S3HS4 and a chip modified with a single helical peptide (LAMGWTNMLY-HHHHHH)-produced no capsaicin response. To the best of our knowledge, S3HS4 is the first example of a synthetic VR mimic peptide. We believe that the present surface-directed structure-based design can be used to exploit the α-helix bundle in hexahistidine-linked bishelical peptides.

The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis.

OBJECTIVES: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD). METHODS: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n = 93, Study 2: n = 99) were retrospectively analyzed. RESULTS: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p < .001). A multiple regression analysis among baseline characteristics revealed that serum calcium (sCa: 8.5-10.5 mg/dL) was associated with an increased LS-BMD by treatment (r2: 0.088, p = .02). While average sCa of the patients was 9.2 mg/dL before treatment, it increased time-dependently to 9.6 mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike's information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3 mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3 mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3 mg/dL (0.8%, p = .038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed. CONCLUSION: sCa was associated with an increased LS-BMD by BPs with aVD.

Changes in caregiving appraisal among family caregivers of persons with dementia: A longitudinal study over 12 months.

AIM: The main purpose of this study was to identify changes in both caregiver burden and positive caregiving appraisal over time, as well as factors affecting these variables. METHODS: This analysis included 41 in-home family caregivers who had completed questionnaires at baseline, 6 months, and 12 months. We assessed various caregiver and care recipient characteristics, caregivers' positive appraisal of caregiving, caregiver burden, desire to continue caregiving, severity of care recipients' cognitive impairment, and behavioural and psychological symptoms of dementia. RESULTS: We observed no significant differences in caregiver burden, positive caregiving appraisal, or behavioural and psychological symptoms of dementia across the three measurement times. However, we did find differences in the desire to continue caregiving and in the personal strain and role strain dimensions of caregiver burden. CONCLUSION: Overall, our study suggests that caregiving service providers should consider support that focuses on improving the subjective caregiving appraisals of caregivers.