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Abstract Background Chest computed tomography findings are helpful for understanding the pathophysiology of severe acute respiratory distress syndrome (ARDS). However, there is no large, multicenter, chest computed tomography registry for patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). The aim of this study was to describe chest computed tomography findings at V-V ECMO initiation and to evaluate the association between the findings and outcomes in severe ARDS. Methods This multicenter, retrospective cohort study enrolled patients with severe ARDS on V-V ECMO, who were admitted to the intensive care units of 24 hospitals in Japan between January 1, 2012, and December 31, 2022. Results The primary outcome was 90-day in-hospital mortality. The secondary outcomes were the successful liberation from V-V ECMO and the values of static lung compliance. Among the 697 registry patients, of the 582 patients who underwent chest computed tomography at V-V ECMO initiation, 394 survived and 188 died. Multivariate Cox regression showed that traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality (hazard ratio [95% confidence interval] 1.77 [1.19–2.63], p = 0.005 and 1.97 [1.02–3.79], p = 0.044, respectively). The presence of traction bronchiectasis was also associated with decreased successful liberation from V-V ECMO (odds ratio: 0.27 [0.14–0.52], p

Background: The human body is regulated by the controlled production and secretion of thousands of chemicals, including polypeptides called cytokines. Cytokines play crucial roles in the immune system reaction following tissue injury and/or body invasion by infectious or non-infectious bodies. They are classified as pro and anti-inflammatory cytokines depending on many factors such as structure and function. Some cytokines mediate inflammatory reactions and contribute to several diseases, such as Rheumatoid arthritis. Very few effective treatment strategies exist to tackle these inflammatory diseases and the available strategies for treatment are also associated with several severe side effects. Although we are in the scientific innovations and medical advancements era, natural compounds are still competing with modern artificial drugs and performing well to effectively treat many diseases without causing side effects. The main purpose of this review is to discuss the effect of some natural compounds on inflammatory cytokine production and elaborate their mode of action further based on already available and recently published literature. Methods: We have reviewed a selected number of natural compounds (Echinacea, Curcumin, Genistein, Eugenol, 6-Gingerol, Thymoquinone, Allicin, Quercetin, Emodin and Parthenolide) that have shown pronounced effects on cytokine production and secretion in several physiological conditions. Findings and Conclusion: Immune cells produce multiple pro-inflammatory and anti-inflammatory cytokines that could be regulated accurately and effectively by using some natural compounds that can block the intracellular machinery and thus reduce cytokine production and secretion. This offers an intriguing background for grasping how these products conduct their activity at a cellular level and sheds light on other natural products to examine efficiency in the same aspect.

Introduction Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%–95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS.Methods and analysis ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%–95% of the target SpO2) or the control (98%–100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1–2 at 90 days after ROSC, to be compared using an intention-to-treat analysis.Ethics and dissemination This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations.Trial registration number UMIN Clinical Trials Registry (UMIN000046914).

Abstract Background Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. Methods A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80–85 mmHg (high-target) and 65–70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients’ condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 μg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. Discussion The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. Trial registration UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

Abstract Background Some academic organizations recommended that physicians intubate patients with COVID-19 with a relatively lower threshold of oxygen usage particularly in the early phase of pandemic. We aimed to elucidate whether early intubation is associated with decreased in-hospital mortality among patients with novel coronavirus disease 2019 (COVID-19) who required intubation. Methods A multicenter, retrospective, observational study was conducted at 66 hospitals in Japan where patients with moderate-to-severe COVID-19 were treated between January and September 2020. Patients who were diagnosed as COVID-19 with a positive reverse-transcription polymerase chain reaction test and intubated during admission were included. Early intubation was defined as intubation conducted in the setting of ≤ 6 L/min of oxygen usage. In-hospital mortality was compared between patients with early and non-early intubation. Inverse probability weighting analyses with propensity scores were performed to adjust patient demographics, comorbidities, hemodynamic status on admission and time at intubation, medications before intubation, severity of COVID-19, and institution characteristics. Subgroup analyses were conducted on the basis of age, severity of hypoxemia at intubation, and days from admission to intubation. Results Among 412 patients eligible for the study, 110 underwent early intubation. In-hospital mortality was lower in patients with early intubation than those with non-early intubation (18 [16.4%] vs. 88 [29.1%]; odds ratio, 0.48 [95% confidence interval 0.27–0.84]; p = 0.009, and adjusted odds ratio, 0.28 [95% confidence interval 0.19–0.42]; p

Background Secondary aortoenteric fistula is a fatal cause of gastrointestinal bleeding after aortic reconstructive surgery with a prosthesis. In most cases, the proximal suture line is involved. We herein report a rare case in which the fistula formed between the suture line of inferior mesenteric artery reimplantation and the jejunum. Case Presentation An 82‐year‐old man was transferred to our hospital due to hematemesis with severe hypovolemic shock. Although he fell into cardiopulmonary arrest, immediate resuscitation achieved return of spontaneous circulation. As his surgical history of aortic reconstruction and computed tomography findings suggested potential secondary aortoenteric fistula, emergency surgery was carried out. The anastomosis between the inferior mesenteric artery and aortic graft was communicating with the jejunum. Partial jejunal resection was undertaken, and the aortic graft was replaced. Conclusion The anastomosis between the inferior mesenteric artery and aortic graft in the previous aortic replacement can become the site of secondary aortoenteric fistula.

Horse-derived ceramide (HC), which contains galactosylceramides as its main component, significantly improves skin symptoms when applied topically to patients with atopic dermatitis. We speculated that efficacy resulted from the amelioration of epidermal ceramide metabolism, and we characterized those effects using reconstructed human epidermal equivalents. Lipid analysis, RT-PCR and Western blotting revealed that HC significantly increased the total ceramide content of the stratum corneum (SC), accompanied by significantly increased gene and/or protein expression levels of ceramide synthase (CERS) 3, fatty acid elongase (ELOVL) 4, glucosylceramide synthase (GCS), β-glucocerebrosidase, sphingomyelin synthase and acid sphingomyelinase. Mechanistic analyses using cultures of primary human keratinocytes revealed the marked stimulatory effects of HC on the mRNA expression levels of CERS3, ELOVL4 and GCS under high calcium-derived differentiation conditions. Signaling analyses demonstrated that an antagonist of PPARβ/δ significantly abrogated the HC-stimulated mRNA expression levels of GCS, CERS3 and ELOVL4. GW9662, an antagonist of PPARγ, significantly abolished the HC-up-regulated mRNA expression levels of GCS and ELOVL4, but not of CERS3. These findings suggest that HC has the distinct potential to accentuate the expression of GCS, CERS3 and ELOVL4 via the activation of PPARβ/δ and/or PPARγ to accelerate ceramide synthesis in the SC.

Staphylococcus aureus is a Gram-positive bacterium that plays a role in the pathogenesis of skin lesions in diabetes mellitus, atopic dermatitis, and psoriasis, all of which are associated with elevated non-enzymatic glycation biomarkers. The production of biofilm protects resident bacteria from host immune defenses and antibiotic interventions, prolonging pathogen survival, and risking recurrence after treatment. Glycated proteins formed from keratin and glucose induce biofilm formation in S. aureus, promoting dysbiosis and increasing pathogenicity. In this study, several glycation-inhibiting and advanced glycation endproduct (AGE) crosslink-breaking compounds were assayed for their ability to inhibit glycated keratin-induced biofilm formation as preliminary screening for clinical testing candidates. Ascorbic acid, astaxanthin, clove extract, n-phenacylthiazolium bromide, and rosemary extract were examined in an in vitro static biofilm model with S. aureus strain ATCC 12600. Near complete biofilm inhibition was achieved with astaxanthin (ED50 = 0.060 mg/mL), clove extract (ED50 = 0.0087 mg/mL), n-phenacylthiazolium bromide (ED50 = 5.3 mg/mL), and rosemary extract (ED50 = 1.5 mg/mL). The dosage necessary for biofilm inhibition was not significantly correlated with growth inhibition (R2 = 0.055. p = 0.49). Anti-glycation and AGE breaking compounds with biofilm inhibitory activity are ideal candidates for treatment of S. aureus dysbiosis and skin infection that is associated with elevated skin glycation.

The Omicron variant (B.529) of COVID-19 caused disease outbreaks worldwide because of its contagious and diverse mutations. To reduce these outbreaks, therapeutic drugs and adjuvant vaccines have been applied for the treatment of the disease. However, these drugs have not shown high efficacy in reducing COVID-19 severity, and even antiviral drugs have not shown to be effective. Researchers thus continue to search for an effective adjuvant therapy with a combination of drugs or vaccines to treat COVID-19 disease. We were motivated to consider melatonin as a defensive agent against SARS-CoV-2 because of its various unique properties. Over 200 scientific publications have shown the significant effects of melatonin in treating diseases, with strong antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has a high safety profile, but it needs further clinical trials and experiments for use as a therapeutic agent against the Omicron variant of COVID-19. It might immediately be able to prevent the development of severe symptoms caused by the coronavirus and can reduce the severity of the infection by improving immunity.

Aim The Bleeding Control Basic (BCon) course was developed by the American College of Surgeons to teach laypeople and health‐care providers (HCPs) how to stop life‐threatening bleeding. The first BCon course in Japan was held for HCPs in July 2018. Our study aimed to evaluate the utility of the course, the satisfaction and confidence level of the HCPs that participated, and their experience with using vascular tourniquets. Method The BCon participants were asked to complete a survey after the BCon courses from December 2018 to December 2019. These participants included different types of HCPs (physicians, nurses, and emergency medical technicians). After the course, the participants were asked to evaluate: (i) the perceived utility of the course, (ii) their satisfaction with the course, (iii) their confidence in the techniques that they learned in the course, (iv) their experience of using tourniquets in eight specific areas using a 10‐point Likert scale. Results A total of 163 HCPs, including 108 physicians, 27 nurses, and 28 emergency medical technicians completed the BCon course. The respondents rated the course highly, showing an average value of approximately 9 for each item for perceived utility, satisfaction, confidence, and experience in using tourniquets. In particular, nurses rated the overall activity more highly than physicians (P

Background The Stop the Bleed (STB) program was developed to bring military bleeding control techniques into wider use among American civilians. It was introduced in Japan in case of mass casualty events during the Tokyo Olympic/Paralympic Games in 2021, and its effectiveness was prospectively evaluated.Methods Japanese physicians certified as STB instructors held bleeding control basic training courses from April to July 2019. Participants’ knowledge was assessed using pre-training and post-training tests comprising five questions. One point was awarded for each correct answer, giving a maximum total score of 5. (Q1) What is the most common preventable trauma death?; (Q2) Which actions should be prioritized for bleeding victims?; (Q3) Which patients should be transferred to hospital first?; (Q4) How should a tourniquet be applied?; (Q5) How should pain associated with a tourniquet be managed?Results The study involved 157 participants (20 physicians/nurses, 82 medical students, 33 emergency services personnel, 22 police officers/security personnel). The mean±SD scores were 2.1±1.1 before training and 3.2±1.0 after training (p

Objective: Elevated levels of serum Nε-carboxymethyllysine (CML), a well-known advanced glycation end-product (AGE), were observed in patients with inflammation or osteoporosis. Astaxanthin was reported to possess anti-inflammatory and antioxidant effects. In the present study, we investigated the effects of commercially available dietary supplement AstaReal ACTR (ASR) capsule content as astaxanthin on CML-HSA-induced inflammatory and receptor activator of nuclear factor-kappa-Β ligand (RANKL)-induced osteoclastogenic gene expression. Methods: RAW 264.7 murine macrophage cells were stimulated with CML-HSA to trigger inflammatory gene expression and treated with either a vehicle control or varied concentrations of astaxanthin. Inflammatory gene expression was measured using an enzyme-linked immunosorbent assay (ELISA) or qPCR. We triggered osteoclastogenesis using RANKL, and osteoclastogenic gene expression was measured through tartrate-resistant acid phosphatase (TRAP) activity, staining, immunofluorescence, and qPCR analyses. Results: CML-HSA showed a stimulatory effect on inflammatory gene expression, and astaxanthin reduced the expression by at least two-fold. The levels of autoinflammatory gene expression were reduced by astaxanthin. The RANKL-induced osteoclastogenesis was significantly inhibited by astaxanthin, with reductions in the activation of nuclear factor-κB (NF-κB), the expression of NFATc1 (nuclear factor of activated T cells 1), multinucleated cell formation, and the expression of mature osteoclast marker genes. Conclusion: Astaxanthin has potential as a remedy for CML-HSA-induced inflammation and RANKL-induced excessive bone loss.

Abstract Semiconductor nanowires with both nano- and micrometre dimensions have been used as effective materials for artificial photosynthesis; however, a single synthesis approach to provide rational control over the macroscopic morphology, which can allow for the high-throughput screening of photocatalytic performance, and carrier transfer between oxide and sulphide nanostructures has been poorly known. Our recent findings indicate that a single parameter, Nb foil thickness, in a vapor-phase synthesis method can alter the macroscopic morphology of resulting Nb2O5 nanowires. Thick Nb foil results in a free-standing Nb2O5 film, whereas a thinner foil leads to fragmentation to give a powder. During the synthesis process, a Rh dopant was provided through metal-organic chemical vapor deposition to reduce the Nb2O5 energy gap. Upon irradiation with visible light (λ > 440 nm), the free-standing nanowire film [Nb2O5:Rh-NW(F)] showed photoanodic current with a Faradaic efficiency of 99% for O2 evolution. Under identical irradiation conditions, the powdered counterpart [Nb2O5:Rh-NW(P)] showed activity for O2 evolution in the presence of an electron acceptor. The poor water-reduction ability was greatly enhanced by the Au-catalysed vapor-liquid-solid (VLS) growth of H2-evolving CdS onto the reduction sites of Nb2O5:Rh-NW(P) [Au/CdS/Nb2O5:Rh-NW(P)].

Abstract The synthesis of silver nanoparticles (AgNPs) within the interlayer space of transparent layered titania nanosheet (TNS) films is investigated. A considerable number of silver ions (≈70% against the cation exchange capacity of the TNS) are intercalated in the TNS films using methyl‐viologen‐containing TNSs as a precursor. The silver ion (Ag+)‐containing TNS films are treated with aqueous sodium tetrahydroborate (NaBH4), resulting in a gradual color change to bright blue. Various structural analyses clearly show that crystalline AgNPs are generated within the interlayer space of the TNSs. The NaBH4‐treated films show intense and characteristic near‐infrared (NIR) extinction spectra up to 1800 nm. The stability of the AgNPs within the TNS against oxygen and moisture is also investigated, and 96% and 82% of the AgNPs remain after standing in air for 1 month and 1 year, respectively. The NIR extinctions of the AgNP‐containing TNS films are further extended by employing different preparation procedures, for example, using sintered TNS films as starting materials and irradiating the Ag+‐containing TNSs with ultraviolet (UV) light. The obtained AgNP‐containing TNS films exhibit photochemical activities in the production of hydrogen from ammonia borane under visible‐light irradiation and the decomposition of nitrogen monoxide under UV‐light irradiation.

Glycation, the nonenzymatic reaction between proteins and excess blood sugar, is implicated in multiple disorders and occurs via the formation and accumulation of advanced glycation end products (AGEs). In our previous studies, we demonstrated that the red-leaf variant of the Persicaria hydropiper sprout (Japanese red water pepper, Benitade) is one of the potent plants that inhibit formation of AGEs. In this study, we aimed to identify antiglycative compounds in Benitade. Benitade extracts were prepared with hot water, then fractionated by using high-performance liquid chromatography (HPLC). The antiglycative efficacy of each fraction was evaluated by measuring the formation of fluorescent AGEs (Ex 370 nm/Em 440 nm). Two fractions, which contained peaks at 26.4 min and 31.8 min, showed potent antiglycative efficacy. When we hydrolyzed these peaks, they shifted to 32.5 and 41.4 min, which are the same retention times as cyanidin and quercetin, respectively. Based on thin-layer chromatography, both compounds contained galactose. Finally, ultrahigh-performance liquid chromatography/quadrupole-time of flight mass spectrometry (UHPLC-QqTOF-MS) analyses were performed to determine the structure of those compounds. Overall, we identified two glycosides, cyanidin 3-O-galactoside (idaein) and quercetin 3-O-galactoside (hyperin), as representative antiglycative compounds in Benitade.