Effect of fentanyl for preterm infants on mechanical ventilation: a systematic review and meta-analysis

Introduction: Because excessive physical stress is harmful, reducing pain and discomfort in premature neonates during mechanical ventilation is a major challenge for physicians. There are no consensus and systematic review on the use of fentanyl, the most commonly used pain reliever in preterm neonates during mechanical ventilation. We aim to compare the benefits and harms of fentanyl versus placebo or no drug for preterm neonates receiving mechanical ventilation. Methods: A systematic review of randomized controlled trials (RCTs) was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The systematic review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Scientific databases such as MEDLINE, Embase, CENTRAL, and CINAHL were searched. All preterm infants on mechanical ventilation and enrolled in an RCT of fentanyl versus control were included. Results: Of 256 reports initially retrieved, 4 reports met the eligibility criteria. Fentanyl was not associated with mortality risk compared to the control (risk ratio: 0.72, 95% confidence intervals [CIs]: 0.36–1.44). No increase in ventilation duration (mean difference [MD]: 0.04, 95% CIs: −0.63–0.71) and no effect on hospital stay length (MD: 4.00, 95% CIs: −7.12–15.12) were found. Fentanyl intervention does not affect any other morbidities, including bronchopulmonary dysplasia, periventricular leukomalacia, patent ductus arteriosus, intraventricular hemorrhage (IVH), severe IVH, sepsis, and necrotizing enterocolitis. Conclusion: The present systematic review and meta-analysis failed to demonstrate the benefit of administering fentanyl to preterm infants on mechanical ventilation in mortality and morbidities. Follow-up studies are required to investigate the long-term neurodevelopment of the children

Transformation of tea catechins and flavonoid glycosides by treatment with Japanese post-fermented tea acetone powder

Japanese post-fermented teas are produced by a combination of aerobic and anaerobic microbial fermentation of the leaves of tea plant. Recently, it was revealed that tea products contain characteristic polyphenols identical to the tea catechin metabolites produced by mammalian intestinal bacteria, such as (2S)-1-(3′,4′,5′-trihydroxyphenyl)-3-(2″,4″,6″-trihydroxyphenyl)-propan-2-ol (EGC-M1). In the present study, degradation of epigallocatechin-3-O-gallate (EGCg) and epigallocatechin (EGC) with acetone powder prepared from Japanese post-fermented tea was examined. Under aerobic conditions, EGCg was hydrolysed to EGC and gallic acid, which were further converted to gallocatechin (GC) and pyrogallol, respectively. Under anaerobic conditions, EGCg was hydrolysed to EGC, which was further metabolised to GC, EGC-M1 and (4R)-5-(3,4,5-trihydroxyphenyl)-4-hydroxypentanoic acid (EGC-M2). Gallic acid was degraded to pyrogallol and then further decomposed. Anaerobic treatment of EGC with the acetone powder yielded EGC-M1, EGC-M2, (4R)-5-(3,4,5-trihydroxyphenyl)-γ-valerolactone, and (4R)-5-(3,4 -dihydroxyphenyl)-γ-valerolactone. Furthermore, similar anaerobic treatment of rutin and hesperidin yielded 3,4-dihydroxyphenylacetic acid and 3-(3,4-dihydroxyphenyl)propanoic acid, respectively

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

Developing a scale to measure nurses' difficulty related to the treatment of gender dysphoric patients

　This study aimed to develop a scale to measure the perceived difficulty experienced by nurses in treating and caring for patients diagnosed with gender dysphoria and examine its reliability and validity. We developed a 26-item preliminary scale through discussions with experts in gender dysphoria treatment. We administered a questionnaire including this scale to 1,010 nurses working at Okayama University Hospital and analyzed the data of 346 nurses who had been involved in the treatment of gender dysphoria and had no missing responses. 　A total of 20 items consisting of two factors, “relationship building” and “negative emotion for gender dysphoria,” were extracted by exploratory factor analysis, and we used them in the final version of the scale. Cronbach's alpha coefficient for the entire scale was 0.879, indicating a high degree of internal consistency. 　However, the correlations with a communication skills scale (ENDCOREs) and the Scale of Gender Conception were limited, and the external validity could not be proven. This scale may be useful for evaluating nursing practice and educational support for nurses; however, there is room for further study on the scale validation

Urine diacetylated spermine might be a nonspecific tumor marker in canine neoplasia

Diacetylated spermine, a polyamine, is clinically used as a tumor marker in human medicine. The purpose of this study was to evaluate the usefulness of diacetylated spermine as a nonspecific tumor marker in dogs. One hundred six dogs were randomly selected and divided into 4 groups (cancer-bearing, n=23; control, n=44; young, n=24; inflammatory, n=15). Urine samples were collected to measure diacetylated spermine and creatinine levels. The diacetylated spermine concentration was determined by enzyme-linked immunoassay, standardized by creatinine concentration. The urine diacetylated spermine concentration was markedly significant elevated in cancer-bearing dogs, as compared to that in control dogs (P=0.0081). Whilst the urine diacetylated spermine level in cancer-bearing group was not markedly different from that in the young group, there was significant different between levels in the control and young groups (P=0.019). No significant difference was observed between the inflammatory and cancer-bearing groups. It is suggested that urine diacetylated spermineis a useful tumor marker in dogs over 2 years of age

Effect of Fentanyl for Preterm Infants on Mechanical Ventilation: A Systematic Review and Meta-Analysis

Introduction: Because excessive physical stress is harmful, reducing pain and discomfort in premature neonates during mechanical ventilation is a major challenge for physicians. There are no consensus and systematic review on the use of fentanyl, the most commonly used pain reliever in preterm neonates during mechanical ventilation. We aim to compare the benefits and harms of fentanyl versus placebo or no drug for preterm neonates receiving mechanical ventilation. Methods: A systematic review of randomized controlled trials (RCTs) was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The systematic review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Scientific databases such as MEDLINE, Embase, CENTRAL, and CINAHL were searched. All preterm infants on mechanical ventilation and enrolled in an RCT of fentanyl versus control were included. Results: Of 256 reports initially retrieved, 4 reports met the eligibility criteria. Fentanyl was not associated with mortality risk compared to the control (risk ratio: 0.72, 95% confidence intervals [CIs]: 0.36–1.44). No increase in ventilation duration (mean difference [MD]: 0.04, 95% CIs: −0.63–0.71) and no effect on hospital stay length (MD: 4.00, 95% CIs: −7.12–15.12) were found. Fentanyl intervention does not affect any other morbidities, including bronchopulmonary dysplasia, periventricular leukomalacia, patent ductus arteriosus, intraventricular hemorrhage (IVH), severe IVH, sepsis, and necrotizing enterocolitis. Conclusion: The present systematic review and meta-analysis failed to demonstrate the benefit of administering fentanyl to preterm infants on mechanical ventilation in mortality and morbidities. Follow-up studies are required to investigate the long-term neurodevelopment of the children

Split conformation of Chaetomium thermophilum Hsp104 disaggregase

Hsp104 and its bacterial homolog ClpB form hexameric ring structures and mediate protein disaggregation. The disaggregated polypeptide is thought to thread through the central channel of the ring. However, the dynamic behavior of Hsp104 during disaggregation remains unclear. Here, we reported the stochastic conformational dynamics and a split conformation of Hsp104 disaggregase from Chaetomium thermophilum (CtHsp104) in the presence of ADP by X-ray crystallography, cryo-electron microscopy (EM), and high-speed atomic force microscopy (AFM). ADP-bound CtHsp104 assembles into a 65 left-handed spiral filament in the crystal structure at a resolution of 2.7 Å. The unit of the filament is a hexamer of the split spiral structure. In the cryo-EM images, staggered and split hexameric rings were observed. Further, high-speed AFM observations showed that a substrate addition enhanced the conformational change and increased the split structure\u27s frequency. Our data suggest that split conformation is an off-pathway state of CtHsp104 during disaggregation