Effects of a Rehabilitation Program Combined with Pain Management That Targets Pain Perception and Activity Avoidance in Older Patients with Acute Vertebral Compression Fracture: a Randomised Controlled Trial

This study aimed to investigate the efect of a rehabilitation program combined with pain management targeting pain perception and activity avoidance on multifaceted outcomes in older patients with acute vertebral compression fractures (VCFs). We randomised 65 older adults with acute VCFs to either an intervention group (n = 32), involving usual rehabilitation combined with pain management that targeted pain perception and activity avoidance, or a control group (n = 33), involving only usual rehabilitation. Te usual rehabilitation was initiated immediately after admission. All patients were treated conservatively. Pain management aimed to improve the patients’ daily behaviour by increasing their daily activities despite pain, rather than by focusing on eliminating the pain. Pain intensity and psychological statuses such as depression, pain catastrophising, and physical activity levels were assessed on admission. Two weeks postadmission and at discharge, physical performance measures were assessed along with the above-given measurements. A signifcant main efect of the group was observed for the intensity of lower back pain, favouring the intervention group (F = 5.135, p = 0.027). At discharge, it was signifcantly better in the intervention group than in the control group (p = 0.011). A time-by-group interaction emerged for magnifcation of the pain catastrophising scale (p = 0.012), physical activity levels (p < 0.001), and six-minute walking distance (p = 0.006), all favouring the intervention group. Rehabilitation programs combined with pain management targeting pain perception and activity avoidance could be an efective conservative treatment for older patients with acute VCFs

Effect of exercise and/or educational interventions on physical activity and pain in patients with hip/knee osteoarthritis: A systematic review with meta-analysis

Objective: To investigate the effectiveness of exercise and/or educational intervention on physical activity and pain in patients with hip/knee osteoarthritis (OA) using systematic review and meta-analysis.Methods: We searched randomized controlled trials that investigated physical activity and pain and compared exercise and/or educational intervention with usual care in patients with hip/knee OA in MEDLINE (PubMed), ProQuest, Scopus, and the Physiotherapy Evidence Database (PEDro), including all those published by April 30, 2022 and written in English. Studies that newly applied analgesics after onset of the intervention were excluded. The revised Cochrane risk-of-bias tool for randomized trials was used to assess the methodological qualities. The random-effects model was used for meta-analysis with standard mean differences using RevMan version 5.4. The body of evidence for each study was synthesized using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.Results: Twenty studies including 2,350 patients were included (7 exercise studies, 8 educational intervention studies and 5 combination studies). The meta-analysis demonstrated that there is very low evidence that combination therapy of exercise and educational intervention improve the physical activity level at the endpoint (4 articles; SMD 0.33, 95% CI 0.04 to 0.51, P = 0.03). Low evidence was observed for combination therapy reducing pain (4 articles; SMD -0.15, 95% CI -0.29 to -0.02, P = 0.03).Discussion: The current evidence indicated that combination therapy of exercise and educational intervention leads to improved physical activity and pain reduction in hip/knee OA patients, but the risk of bias in each study, especially in allocation concealment, downgraded the evidence level. These findings support the use of a combination therapy of exercise and educational intervention to promote physical activity levels in patients with hip/knee OA.Trail registration: There was no financial support for this research. The protocol was registered at the International Prospective Register of Systematic Reviews (registration code: CRD42020205804)

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

Great apes’ understanding of biomechanics: eye-tracking experiments using three-dimensional computer-generated animations

Visual processing of the body movements of other animals is important for adaptive animal behaviors. It is widely known that animals can distinguish articulated animal movements even when they are just represented by points of light such that only information about biological motion is retained. However, the extent to which nonhuman great apes comprehend the underlying structural and physiological constraints affecting each moving body part, i.e., biomechanics, is still unclear. To address this, we examined the understanding of biomechanics in bonobos (Pan paniscus) and chimpanzees (Pan troglodytes), following a previous study on humans (Homo sapiens). Apes underwent eye tracking while viewing three-dimensional computer-generated (CG) animations of biomechanically possible or impossible elbow movements performed by a human, robot, or nonhuman ape. Overall, apes did not differentiate their gaze between possible and impossible movements of elbows. However, some apes looked at elbows for longer when viewing impossible vs. possible robot movements, which indicates that they may have had knowledge of biomechanics and that this knowledge could be extended to a novel agent. These mixed results make it difficult to draw a firm conclusion regarding the extent to which apes understand biomechanics. We discuss some methodological features that may be responsible for the results, as well as implications for future nonhuman animal studies involving the presentation of CG animations or measurement of gaze behaviors

Microstructural Observation and Mechanical Property Evaluation of Plastic Parts Obtained by Preheat Free Laser Sintering

Tensile test on preheat free (PF) processed part was performed it is shown that ultimate strength is the same as that from conventional process when relative density is the same. Microstructural observation showed that decomposition occurs during PF process. Microstructure of PF processed part is similar to those of amorphous. It is indicated that preheat free process can improve geometrical precision. PGA to which conventional process cannot be applied was successful processed by PF. Tensile test on preheat free (PF) processed part was performed it is shown that ultimate strength is the same as that from conventional process when relative density is the same. Microstructural observation showed that decomposition occurs during PF process. Microstructure of PF processed part is similar to those of amorphous. It is indicated that preheat free process can improve geometrical precision. PGA to which conventional process cannot be applied was successful processed by PF.Mechanical Engineerin

Characterization and Utilization of Disulfide-Bonded SARS-CoV-2 Receptor Binding Domain of Spike Protein Synthesized by Wheat Germ Cell-Free Production System

The spike protein (SP) of SARS-CoV-2 is an important target for COVID-19 therapeutics and vaccines as it binds to the ACE2 receptor and enables viral infection. Rapid production and functional characterization of properly folded SP is of the utmost importance for studying the immunogenicity and receptor-binding activity of this protein considering the emergence of highly infectious viral variants. In this study, we attempted to express the receptor-binding region (RBD) of SARS-CoV-2 SP containing disulfide bonds using the wheat germ cell-free protein synthesis system. By adding protein disulfide isomerase (PDI) and endoplasmic reticulum oxidase (ERO1α) to the translational reaction mixture, we succeeded in synthesizing a functionally intact RBD protein that can interact with ACE2. Using this RBD protein, we have developed a high-throughput AlphaScreen assay to evaluate the RBD–ACE2 interaction, which can be applied for drug screening and mutation analysis. Thus, our method sheds new light on the structural and functional properties of SARS-CoV-2 SP and has the potential to contribute to the development of new COVID-19 therapeutics