Reliability and validity of the patient disability-oriented diagnostic nomenclature system for prosthetic dentistry

Purpose: The Japan Prosthodontic Society (JPS) has proposed a new diagnostic nomenclature system (DNS), based on pathogenesis and etiology, to facilitate and improve prosthodontic treatment. This systemspecifies patient disability and the causative factor (i.e. ‘‘B (disability) caused by A (causative factor)’’). The purpose of this study was to examine the reliability and validity of this DNS. Study selection: The JPS Clinical Guideline Committee assessed mock patient charts and formulated disease names using the new DNS. Fifty validators, comprising prosthodontic specialists and dental residents, made diagnoses using the same patient charts. Reliability was evaluated as the consistency of the disease names among the validators, and validity was evaluated using the concordance rate of the disease names with the reference disease names. Results: Krippendorff’s α was 0.378 among all validators, 0.370 among prosthodontic specialists, and 0.401 among dental hospital residents. Krippendorff’s α for 10 validators (3 specialists and 7 residents) with higher concordance rates was 0.524. Two validators (1 specialist and 1 resident) with the highest concordance rates had a Krippendorff’s α of 0.648. Common disease names had higher concordance rates, while uncommon disease names showed lower concordance rates. These rates did not show correlation with clinical experience of the validator or time taken to devise the disease name. Conclusions: High reliability was not found among all validators; however, validators with higher concordance rates showed better reliability. Furthermore, common disease names had higher concordance rates. These findings indicate that the new DNS for prosthodontic dentistry exhibits clinically acceptable reliability and validity

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

Strain-induced significant increase in metal-insulator transition temperature in oxygen-deficient Fe oxide epitaxial thin films

Oxygen coordination of transition metals is a key for functional properties of transition-metal oxides, because hybridization of transition-metal d and oxygen p orbitals determines correlations between charges, spins and lattices. Strain often modifies the oxygen coordination environment and affects such correlations in the oxides, resulting in the emergence of unusual properties and, in some cases, fascinating behaviors. While these strain effects have been studied in many of the fully-oxygenated oxides, such as ABO3 perovskites, those in oxygen-deficient oxides consisting of various oxygen coordination environments like tetrahedra and pyramids as well as octahedra remain unexplored. Here we report on the discovery of a strain-induced significant increase, by 550 K, in the metal-insulator transition temperature of an oxygen-deficient Fe oxide epitaxial thin film. The observed transition at 620 K is ascribed to charge disproportionation of Fe 3.66+ into Fe 4+ and Fe 3+, associated with oxygen-vacancy ordering. The significant increase in the metal-insulator transition temperature, from 70K in the bulk material, demonstrates that epitaxial growth of oxygen-deficient oxides under substrate-induced strain is a promising route for exploring novel functionality

Effect of (−)-Epigallocatechin Gallate to Staphylococcal Enterotoxin A on Toxin Activity

Staphylococcal enterotoxin A (SEA) functions both as superantigens that stimulate non-specific T cell proliferation as well as potent gastrointestinal toxins. We previously reported that (−)-epigallocatechin gallate (EGCG) binds to SEA. Therefore, the ability of EGCG to inhibit SEA toxin activity was examined. As a result, EGCG significantly decreased SEA-induced expression and production of interferon gamma (IFN-γ). In addition, EGCG inhibited SEA-induced spleen cell proliferation. To investigate the role of the galloyl group in EGCG on SEA cytotoxicity in more detail, the effect of the binding of a hydroxyl group at position 3 of the galloyl group in EGCG to SEA on SEA cytotoxicity was examined using two methylated EGCG. SEA cytotoxicity was significantly controlled in both (−)-3′′-Me-EGCG and (−)-4′′-Me-EGCG. These results suggest that EGCG inhibits toxic activity via direct interaction with SEA or without any interaction with SEA. The binding affinity between SEA and EGCG under in vivo conditions was examined using a model solution. Although after treatment under acidic and alkaline conditions, the presence of protein and the digestive tract model solution, EGCG still interacted with SEA. Our studies are the first to demonstrate the effect of the binding of EGCG to SEA on toxin activity

Binding of Catechins to Staphylococcal Enterotoxin A

Staphylococcal enterotoxin A (SEA) is a toxin protein, and is the most common cause of staphylococcal food poisoning. Polyphenols, such as catechins, are known to interact with proteins. In this study, we investigated the binding of catechins to SEA using SPR (Biacore), Fourier transform infrared spectroscopy (FT-IR), isothermal titration calorimetry (ITC), and protein-ligand docking. We found that (−)-epigallocatechin gallate (EGCG) could strongly bind to SEA. According to thermodynamic parameters, a negative ΔG indicated that the interaction between EGCG and SEA was spontaneous, and the electrostatic force accompanied by hydrophobic binding forces may play a major role in the binding. Data from Western blot analysis and docking simulation suggest that the hydroxyl group at position 3 of the galloyl group in the catechin structure was responsible for binding affinity with the Y91 of the A-6 region of SEA active sites. Our results provide further understanding of the binding interactions between catechins and SEA, and the inhibition of toxin activities by catechins

Stretching before sleep reduces the frequency and severity of nocturnal leg cramps in older adults: a randomised trial

QUESTION: In adults who experience nocturnal leg cramps, does stretching of the calf and hamstring muscles each day just before sleep reduce the frequency and severity of the cramps? DESIGN: A randomised trial with concealed allocation and intention-to-treat analysis. PARTICIPANTS: Eighty adults aged over 55 years with nocturnal leg cramps who were not being treated with quinine. INTERVENTION: The experimental group performed stretches of the calf and hamstring muscles nightly, immediately before going to sleep, for six weeks. The control group performed no specific stretching exercises. Both groups continued other usual activities. OUTCOME MEASURES: Participants recorded the frequency of nocturnal leg cramps in a daily diary. Participants also recorded the severity of the pain associated with nocturnal leg cramps on a 10-cm visual analogue scale. Adverse events were also recorded. RESULTS: All participants completed the study. At six weeks, the frequency of nocturnal leg cramps decreased significantly more in the experimental group, mean difference 1.2 cramps per night (95% CI 0.6 to 1.8). The severity of the nocturnal leg cramps had also decreased significantly more in the experimental group than in the control group, mean difference 1.3 cm (95% CI 0.9 to 1.7) on the 10-cm visual analogue scale. CONCLUSION: Nightly stretching before going to sleep reduces the frequency and severity of nocturnal leg cramps in older adults. TRIAL REGISTRATION: NCT01421628