Challenges in decision-making support processes regarding living kidney donation: A qualitative study

Wada Y., Ueno T., Umeshita K., et al. Challenges in decision-making support processes regarding living kidney donation: A qualitative study. Journal of Renal Care , (2024); https://doi.org/10.1111/jorc.12494.Background: Previous studies on decision-making of living kidney donors have indicated issues regarding donors' autonomy is inherent in decision-making to donate their kidney. Establishing effective decision-making support that guarantees autonomy of living kidney donor candidates is important. Objectives: The aim of this study was to identify the difficulties in the decision-making support when clinical transplant coordinators advocating for the autonomy of donor candidates of living donor kidney transplantation and to identify the methods to deal with these difficulties. Design: A qualitative descriptive study. Participants: Ten clinical transplant coordinators supporting living kidney donors. Approach: Semi-structured interviews were conducted using an interview guide. The modified grounded theory approach was utilised to analyse. Results: Three categories related to difficulties were as follows: issues inherent to the interaction between coordinators, donor candidates and their families; issues regarding the environment and institutional background in which coordinators operate; and emotional labour undertaken by coordinators in the decision-making support process. Additionally, five categories related to methods were as follows: assessing the autonomy of donor candidates based on the coordinators nursing experience; interventions for the donor candidates and their family members based on the coordinators nursing experience; smooth coordination with medical staff; clarifying and asserting their views as coordinators; and readiness to protect the donor candidates. Conclusion: The involvement of highly experienced coordinators with excellent and assertive communication skills as well as the ability to reflect on their own practices is essential. Moreover, we may need to fundamentally review the transplant community, where power domination is inherent

Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model

<p>Abstract</p> <p>Background</p> <p>To determine whether oral administration of geranylgeranylacetone (GGA), a nontoxic anti-ulcer drug that is an inducer of heat shock protein (HSP) 70, protects against drug-induced lung injury/fibrosis <it>in vivo</it>.</p> <p>Methods</p> <p>We used a bleomycin (BLM)-induced lung fibrosis model in which mice were treated with oral 600 mg/kg of GGA before and after BLM administration. Inflammation and fibrosis were evaluated by histological scoring, hydroxyproline content in the lung and inflammatory cell count, and quantification by ELISA of macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid. Apoptosis was evaluated by the TUNEL method. The induction of HSP70 in the lung was examined with western blot analysis and its localization was determined by immunohistochemistry.</p> <p>Results</p> <p>We confirmed the presence of inflammation and fibrosis in the BLM-induced lung injury model and induction of HSP70 by oral administration of GGA. GGA prevented apoptosis of cellular constituents of lung tissue, such as epithelial cells, most likely related to the <it>de novo </it>induction of HSP70 in the lungs. GGA-treated mice also showed less fibrosis of the lungs, associated with the findings of suppression of both production of MIP-2 and inflammatory cell accumulation in the injured lung, compared with vehicle-treated mice.</p> <p>Conclusion</p> <p>GGA had a protective effect on drug-induced lung injury/fibrosis. Disease-modifying antirheumatic drugs such as methotrexate, which are indispensable for the treatment of rheumatoid arthritis, often cause interstitial lung diseases, an adverse event that currently cannot be prevented. Clinical use of GGA for drug-induced pulmonary fibrosis might be considered in the future.</p

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Effect of connection induced upper body movements on embodiment towards a limb controlled by another during virtual co-embodiment.

Even if we cannot control them, or when we receive no tactile or proprioceptive feedback from them, limbs attached to our bodies can still provide indirect proprioceptive and haptic stimulations to the body parts they are attached to simply due to the physical connections. In this study we investigated whether such indirect movement and haptic feedbacks from a limb contribute to a feeling of embodiment towards it. To investigate this issue, we developed a 'Joint Avatar' setup in which two individuals were given full control over the limbs in different sides (left and right) of an avatar during a reaching task. The backs of the two individuals were connected with a pair of solid braces through which they could exchange forces and match the upper body postures with one another. Coupled with the first-person view, this simulated an experience of the upper body being synchronously dragged by the partner-controlled virtual arm when it moved. We observed that this passive synchronized upper-body movement significantly reduced the feeling of the partner-controlled limb being owned or controlled by another. In summary, our results suggest that even in total absence of control, connection induced upper body movements synchronized with the visible limb movements can positively affect the sense of embodiment towards partner-controlled or autonomous limbs