Wearable dummy to simulate equinovarus for training of physical therapists

Abstract: It is indispensable for physical therapists in training to experience various symptoms during their period of education; however, such chances are limited in educational institutions. We developed a prototype of a wearable dummyrobot system to simulate equinovarus, which is a typical disorder of the foot caused by stroke, to enhance the training of physical therapists (PTs). This wearable dummy system makes it possible to simulate joint disorders, while allowing the trainees to learn about the complex joint movements of humans, such as those observed in human feet. The dummy system deforms the foot of a healthy wearer using a wire mechanism so that the resultant foot posture and resistance force required for therapeutic operations resemble those of typical equinovarus patients. The resistance forces felt by the trainees can be tuned by changing the endpoint of the wire. From sensory evaluations involving PTs, it was concluded that with potential future improvements, the dummy simulator will become an effective training tool to aid physical therapy students

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

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

Assessment of robotic patient simulators for training in manual physical therapy examination techniques.

Robots that simulate patients suffering from joint resistance caused by biomechanical and neural impairments are used to aid the training of physical therapists in manual examination techniques. However, there are few methods for assessing such robots. This article proposes two types of assessment measures based on typical judgments of clinicians. One of the measures involves the evaluation of how well the simulator presents different severities of a specified disease. Experienced clinicians were requested to rate the simulated symptoms in terms of severity, and the consistency of their ratings was used as a performance measure. The other measure involves the evaluation of how well the simulator presents different types of symptoms. In this case, the clinicians were requested to classify the simulated resistances in terms of symptom type, and the average ratios of their answers were used as performance measures. For both types of assessment measures, a higher index implied higher agreement among the experienced clinicians that subjectively assessed the symptoms based on typical symptom features. We applied these two assessment methods to a patient knee robot and achieved positive appraisals. The assessment measures have potential for use in comparing several patient simulators for training physical therapists, rather than as absolute indices for developing a standard

Chemical toxicity of indocyanine green damages retinal pigment epithelium. Invest Ophthalmol Vis Sci.

PURPOSE. To investigate the chemical toxicity of indocyanine green (ICG). METHODS. Surface active and precipitating effects of ICG were quantitatively analyzed by determining bovine serum albumin dissolved or precipitated in the presence or absence of salt solutions. The effects of precipitation on serum and cytotoxicity were evaluated by measuring the viability of retinal pigment epithelium (RPE) in vitro. RESULTS. ICG functioned as a surfactant without salts, but with nearly physiological concentrations of balanced salts, it functioned as a unique precipitating factor. This rendered the soluble molecules in serum that are indispensable in the culture of RPE cells insoluble during a 12-hour exposure, resulting in poor cell survival in vitro. Cytotoxicity in serum-free medium was also shown during brief exposures. CONCLUSIONS. Commonly used dosages of ICG directly applied into the vitreous cavity, which not only contact the retina but also invade the space between the retina and RPE through a macular hole, may be sufficient to induce retinal disorders after the damaging chemical property of ICG has disturbed the microenvironment. (Invest Ophthalmol Vis Sci. 2005;46: 2531-2539) DOI:10.1167/iovs.04-1521 B efore 1990, there was no treatment available for macular holes. Kelly and Wendel 1 first reported that vitreous surgery improved visual acuity in some eyes with macular holes, and since then an effective internal limiting membrane (ILM) peeling technique has been used to improve outcomes. 2 However, it is generally very difficult to perform efficient and complete removal of the ILM, because the ILM is thin and transparent. After indocyanine green (ICG) was introduced for selective staining of the ILM, 3 ICG-facilitated ILM peeling appeared to be beneficial, because it facilitated functional and anatomic success. 4 -10 Although some reports have shown no negative effects and/or excellent anatomic results and visual retinal function after ICG-assisted ILM peeling for macular hole surgery, 18,21 Unusual atrophic changes in the retinal pigment epithelium (RPE) at the site of the macular hole and undesirable postoperative visual acuity were reported, despite successful anatomic closure of the macular hole. 22 After macular hole surgery with ICG-guided ILM peeling, hypertrophic and atrophic RPE changes were apparent. 26 ICG injected into the vitreous cavity showed b-and a-wave amplitude, and latency abnormalities, suggesting impairment of retinal function. 27 ICG caused cytotoxicity in cultured RPE cells in a dose-and time-dependent manner, and necrotic cell death occurred. 29 ICG injected into the subretinal space caused destructive degeneration of photoreceptors and RPE, 32 Although all these data obviously indicate toxic effects of ICG on retinal function, we hardly consider these results to be caused by ICG alone. ICG-induced cytotoxicity in cultured RPE was reduced with the removal of sodium from the solvent. 33 Toxic effects of ICG on cultured RPE cells have been related to osmolarity of the solvent. 34 Factors such as sodium or osmolarity modulate the degree of toxicity, implying that some chemical mechanisms may be involved in the effects. The dye ICG is an amphipathic molecule and has both hydrophilic (two anions and one ammonium cation) and hydrophobic (mainly aromatic series) properties, suggesting that ICG is a surface active compound and may have unknown chemical and toxic properties that affect the retina. In the present study, we demonstrated unique chemical properties of ICG-acting as a precipitating factor in the presence of salts, but as a surface active compound in the absence of salts. Our data support the proposition that the clinically used dosage of ICG in buffered salt conditions directly applied into the vitreous cavity and subretinal space through a macular hole may be sufficient to induce retinal disorder. From th

Sample resistance torques and knee angular velocities of the five types of simulated symptoms.

<p>The black and gray curves respectively represent the measured and set torques. <i>e</i>_r indicates the maximum and mean errors between the two values. Overall, the measured torques are in adequate agreement with the set values.</p