Verifying the validity and reliability of the Japanese version of the Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Scale

BackgroundPediatric patients, especially in the preverbal stage, cannot self-report intensity of pain therefore several validated observational tools, including the Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Scale, have been used as a benchmark to evaluate pediatric pain. Unfortunately, this scale is currently unavailable in Japanese, precluding its widespread use in Japanese hospitals.ObjectivesTo translate and verify the validity and reliability of the Japanese version of the FLACC Behavioral Scale.MethodBack-translation was first conducted by eight medical researchers, then an available sample of patients at the University of Tsukuba Pediatric Intensive Care Unit (from May 2017 to August 2017) was enrolled in a clinical study. Two researchers evaluated the validity of the translated FLACC Behavioral Scale by weighted kappa coefficient and intraclass correlation coefficients (ICC). Observational pain was simultaneously measured by the visual analog scale (VAS obs) and reliability was evaluated by correlation analysis.ResultThe original author approved the translation. For the clinical study, a total of 121 observations were obtained from 24 pediatric patients. Agreement between observers was highly correlated for each of the FLACC categories (Face: κ = 0.85, Leg: κ = 0.74, Activity: κ = 0.89, Cry: κ = 0.93, Consolability: κ = 0.93) as well as the total score (Total: κ = 0.95,). Correlation analysis demonstrated a good criterion validation between the FLACC scale and the VAS obs. (r = 0.96)ConclusionOur Japanese version of the FLACC Behavioral Scale shows high validity and reliability

Verifying the Japanese version of the Preschool Confusion Assessment Method for the ICU (psCAM‐ICU)

AimPediatric delirium has been well investigated and its prevalence is reported to be from 20% to 44%. For pediatric intensive care settings, several validated assessment tools for diagnosing delirium, including the Preschool Confusion Assessment Method for the Intensive Care Unit (psCAM‐ICU), are available in English. However, validated assessment tools for identifying pediatric delirium are unavailable in Japanese. Therefore, the aim of this study is to verify the Japanese translation of the psCAM‐ICU.MethodsWe enrolled patients at the Pediatric ICU at University of Tsukuba Hospital (Tsukuba, Japan) from May 2017 to February 2019. Enrollment criteria included patients aged 6 months to 5 years, and we excluded coma patients scoring under −4 on the Richmond Agitation–Sedation Scale or suffering from stroke. Pediatric patient delirium was simultaneously evaluated by three medical workers (pediatric intensivist and researchers). Psychiatrists then verified these findings against criteria of the Diagnostic and Statistical Manual of Mental Disorders – 5th Edition. We evaluated criterion validity (sensitivity and specificity) and reliability using Cohen\u27s κ coefficient.ResultsWe made a total of 56 independent assessments of 19 patients (42% female) with an average age of 18 (±15) weeks. Mechanical ventilation was used at least once in 73% of patients and the positive rate of delirium was 54% in total observation. Overall, the psCAM‐ICU showed high sensitivity, specificity (sensitivity, 0.90 [95% confidence interval [CI], 0.80–0.94]; specificity, 0.93 [95% CI, 0.83–0.97]), and high reliability within the researcher assessments (κ = 0.92; 95% CI, 0.82–1.0).ConclusionWe verified the psCAM‐ICU and it shows high validity and reliability

Fish oil constituent eicosapentaenoic acid inhibits endothelin-induced cardiomyocyte hypertrophy via PPAR-α

AimsA growing body of evidence shows the cardiovascular benefits of fish oil ingredients, including eicosapentaenoic acid (EPA), in humans and experimental animals. However, the effects of EPA on endothelin (ET)-1-induced cardiomyocyte hypertrophy and the involved signaling cascade are largely unknown. A previous study has demonstrated that peroxisomal proliferator-activated receptor (PPAR)-α ligand (fenofibrate) prevents ET-1-induced cardiomyocyte hypertrophy. Although EPA is a ligand of PPAR-α, to date, no study has examined a relationship between EPA and PPAR-α in cardiomyocyte hypertrophy. Here, we investigated whether EPA can block ET-1-induced cardiomyocyte hypertrophy and the possible underlying mechanisms.Main methodsAt day 4 of culture, neonatal rat cardiomyocytes were divided into four groups: control, control cells treated with EPA (10 μM), ET-1 (0.1 nM) administered only and EPA-pre-treated ET-1 administered groups. Also, the cardiomyocytes were treated with PPAR-α siRNA in order to elucidate the mechanisms that may underlie suppression of hypertrophy via the EPA-PPAR system.Key findingsFollowing ET-1 treatment, 2.12- and 1.92-fold increases in surface area and total protein synthesis rate in cardiomyocytes, respectively, were observed and these changes were greatly blocked by EPA pre-treatment. Further, the expression of PPAR-α increased in EPA-treated groups. PPAR-PPRE binding activity was suppressed in ET-1 administered cardiomyocyte and this suppression was improved by EPA treatment. Lastly, pre-treatment of cardiomyocytes with PPAR-α siRNA prior to EPA treatment attenuated the suppressing effects of EPA on cardiomyocyte hypertrophy.SignificanceIn conclusion, the present study shows that EPA attenuates ET-1 induced cardiomyocyte hypertrophy by up regulating levels of PPAR-α pathway

敗血症超急性期モデル動物に対するTEMPO-RNPを用いた抗酸化ストレス療法

科学研究費助成事業 研究成果報告書：基盤研究(C)2014-2016課題番号 : 2646274

Severe COVID-19 Infection Associated with Endothelial Dysfunction Induces Multiple Organ Dysfunction: A Review of Therapeutic Interventions

Since December 2019, the SARS-CoV-2 (COVID-19) pandemic has transfixed the medical world. COVID-19 symptoms vary from mild to severe and underlying chronic conditions such as pulmonary/cardiovascular disease and diabetes induce excessive inflammatory responses to COVID-19 and these underlying chronic diseases are mediated by endothelial dysfunction. Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients, but coagulation induced by excessive inflammation, thrombosis, and disseminated intravascular coagulation (DIC) also induce death by multiple-organ dysfunction syndrome. These associations imply that maintaining endothelial integrity is crucial for favorable prognoses with COVID-19 and therapeutic intervention to support this may be beneficial. Here, we summarize the extent of heart injuries, ischemic stroke and hemorrhage, acute kidney injury, and liver injury caused by immune-mediated endothelial dysfunction that result in the phenomenon of multi-organ dysfunction seen in COVID-19 patients. Moreover, the potential therapeutic effect of angiotensin receptor blockers and angiotensin-converting enzyme inhibitors that improve endothelial dysfunction as well as the bradykinin storm are discussed

Effects of aerobic exercise training on circulating angiopoietin-like protein 2 in overweight and obese men: a pilot study

Background and objective: Angiopoietin-like protein 2 (ANGPTL2) is a pro-inflammatory adipokine that is upregulated in obesity and plays a role in the progression of cardiometabolic diseases, including diabetes and atherosclerosis. Aerobic exercise is one of the effective strategies for reducing the levels of various pro-inflammatory biomolecules in obese individuals. However, the effects of aerobic exercise training on circulating ANGPTL2 levels in obese individuals remain unclear. The objective of this study was to investigate the effect of aerobic exercise training on serum ANGPTL2 levels in overweight and obese men. Material and methods: Twenty overweight and obese men (age, 49 ±10 years; body mass index, 27.4 ± 2.2 kg/m2) completed a 12-week aerobic exercise training program (60–85% Heart ratem⁢a⁢x, 40–60 min/day, 3 days/week). Before and after the exercise program, serum ANGPTL2 levels were measured using the enzyme-linked immunosorbent assay. Daily step counts and the different physical activities based on the intensity were assessed using a triaxial accelerometer. Results: Serum ANGPTL2 levels were significantly decreased after the 12-week aerobic exercise training program ((3.0 ± 0.6) vs. (2.7 ± 0.7) ng/mL, P < 0.05). Daily step counts ((8362 ± 4551) vs. (10357 ± 3168) steps/day, P < 0.05) and moderate- to vigorous-intensity physical activity (MVPA) time ((58 ± 45) vs. (76 ± 37) min/day, P < 0.001) were significantly increased after the exercise intervention. The changes in serum ANGPTL2 levels were negatively correlated with corresponding changes in daily step counts (partial r = –0.49, P < 0.05) and MVPA time (partial r = –0.47, P < 0.05) after adjustment for age and accelerometer wear time. Conlcusion: These findings collectively suggest that aerobic exercise training, in particular an increase in MVPA, can be associated with decreased circulating levels of ANGPTL2 in overweight and obese men