Efficacy of soft palatal augmentation prosthesis for oral functional rehabilitation in patients with dysarthria and dysphagia: a protocol for a randomised controlled trial

Introduction Palatal augmentation prosthesis (PAP) is used in patients with articulation and swallowing disorders caused by postoperative loss of tongue tissue due to tongue cancer, cerebrovascular disease sequelae and age-related hypofunction. We have previously reported a newly designed soft PAP fabricated using an thermoplastic material that is particularly appropriate for early intervention. However, the effect of soft PAP on oral function improvement remains to be elucidated. The aim of this study is to investigate whether soft PAP can improve dysarthria and dysphagia occurring as cerebrovascular disease sequelae. Methods and analysis This prospective, randomised, controlled trial will compare the immediate and training effects of rehabilitation using soft PAP with those of rehabilitation without using it. Primary outcomes are the single-word intelligibility test score and pharyngeal transit time (PTT). Secondary outcomes are tongue function (evaluated based on maximum tongue pressure, repetitions of tongue pressure and endurance of tongue pressure), articulation function (evaluated based on speech intelligibility, oral diadochokinesis, Voice-Related Quality of Life (V-RQOL)) and swallowing function (evaluated using Eating Assessment Tool-10). The study results will help determine the efficacy of Soft PAP in improving functional outcomes of word intelligibility and PTT. We hypothesised that early rehabilitation using Soft PAP would more effectively improve articulation and swallowing function compared with conventional rehabilitation without using soft PAP. Ethics and dissemination Ethical approval was obtained from the Okayama University Certified Review Board. The study findings will be published in an open access, peer-reviewed journal and presented at relevant conferences and research meetings

Person-centered dementia care during COVID-19: a qualitative case study of impact on and collaborations between caregivers

BackgroundLittle is known about the actual impact of COVID-19 on caregivers of older people with dementia and resultant collaborations among them to provide continued person-centered care while undertaking infection control measures. In this study, we explored the impact of providing dementia care during COVID-19 on caregivers involved in dementia care.MethodsThis is an exploratory qualitative case study. The participants were family members living with older people with dementia, care managers, and the medical and long-term care facility staff. Data were collected from 46 caregivers via face-to-face and semi-structured interviews and analyzed using thematic analysis.ResultsThe interviews identified 22 themes related to the impact of COVID-19 on different positions of the caregivers involved in dementia care and their collaboration, and we categorized them into six categories. The core themes were “re-acknowledgement of care priorities” and “rebuilding of relationships.” When caregivers’ perceptions were aligned in the decision-making processes regarding care priorities, “reaffirmation of trust” and “strengthening of intimate relationships” emerged as positive changes in their relationships. Furthermore, the differences in the ability of each caregiver to access and select correct and appropriate information about COVID-19, and the extent of infection spread in the region were related to “anxiety during COVID-19 pandemic” and caused a “gap in perception” regarding infection control.ConclusionsThe present study clarified that the process of aligning the perceptions of caregivers to the objectives and priorities of care for older people with dementia during COVID-19 pandemic strengthened the relationships among caregivers. The findings of this study are useful for caregivers involved in person-centered dementia care

CO(JJ=1-0) mapping survey of 64 galaxies in the Fornax cluster with the ALMA Morita array

We conduct a $^{12}$C$^{16}$O($J$=1-0) (hereafter CO) mapping survey of 64 galaxies in the Fornax cluster using the ALMA Morita array in cycle 5. CO emission is detected from 23 out of the 64 galaxies. Our sample includes dwarf, spiral and elliptical galaxies with stellar masses of $M_{\rm star}\sim10^{6.3-11.6}$~M$_\odot$. The achieved beam size and sensitivity are $15''\times8''$ and $\sim12$~mJy~beam$^{-1}$ at the velocity resolution of $\sim10$~km~s$^{-1}$, respectively. We study the cold-gas (molecular- and atomic-gas) properties of 38 subsamples with $M_{\rm star}>10^9$~M$_\odot$ combined with literature HI data. We find that: (1) the low star-formation (SF) activity in the Fornax galaxies is caused by the decrease in the cold-gas mass fraction with respect to stellar mass (hereafter, gas fraction) rather than the decrease of the SF efficiency from the cold gas; (2) the atomic-gas fraction is more heavily reduced than the molecular-gas fraction of such galaxies with low SF activity. A comparison between the cold-gas properties of the Fornax galaxies and their environmental properties suggests that the atomic gas is stripped tidally and by the ram pressure, which leads to the molecular gas depletion with an aid of the strangulation and consequently SF quenching. Pre-processes in the group environment would also play a role in reducing cold-gas reservoirs in some Fornax galaxies.Comment: 53 pages, 41 figures, accepted for publication in ApJ

Reconstructing the Inflaton Potential --- an Overview

We review the relation between the inflationary potential and the spectra of density (scalar) perturbations and gravitational waves (tensor perturbations) produced, with particular emphasis on the possibility of reconstructing the inflaton potential from observations. The spectra provide a potentially powerful test of the inflationary hypothesis; they are not independent but instead are linked by consistency relations reflecting their origin from a single inflationary potential. To lowest-order in a perturbation expansion there is a single, now familiar, relation between the tensor spectral index and the relative amplitude of the spectra. We demonstrate that there is an infinite hierarchy of such consistency equations, though observational difficulties suggest only the first is ever likely to be useful. We also note that since observations are expected to yield much better information on the scalars than on the tensors, it is likely to be the next-order version of this consistency equation which will be appropriate, not the lowest-order one. If inflation passes the consistency test, one can then confidently use the remaining observational information to constrain the inflationary potential, and we survey the general perturbative scheme for carrying out this procedure. Explicit expressions valid to next-lowest order in the expansion are presented. We then briefly assess the prospects for future observations reaching the quality required, and consider a simulated data set that is motivated by this outlook.Comment: 69 pages standard LaTeX plus 4 postscript figures. Postscript version of text in landscape format (35 pages) available at http://star-www.maps.susx.ac.uk/papers/infcos_papers.html Modifications are a variety of updates to discussion and reference

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