Chest CT findings in severe acute respiratory distress syndrome requiring V-V ECMO: J-CARVE registry.

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 < 0.001). Lower static lung compliance was associated with some chest computed tomography findings related to changes outside of pulmonary opacity, but not with the findings related to pulmonary opacity. CONCLUSIONS: Traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality in patients with severe ARDS who required V-V ECMO.

Association of Contrast Extravasation Grade With Massive Transfusion in Pediatric Blunt Liver and Spleen Injuries: A Multicenter Retrospective Cohort Study.

BACKGROUND: This study aimed to assess whether the grade of contrast extravasation (CE) on CT scans was associated with massive transfusion (MT) requirements in pediatric blunt liver and/or spleen injuries (BLSI). METHODS: This multicenter retrospective cohort study included pediatric patients (≤16 years old) who sustained BLSI between 2008 and 2019. MT was defined as transfusion of all blood products ≥40 mL/kg within the first 24 h of admission. Associations between CE and MT requirements were assessed using multivariate logistic regression analysis with cluster-adjusted robust standard errors to calculate the adjusted odds ratio (AOR). RESULTS: A total of 1407 children (median age: 9 years) from 83 institutions were included in the analysis. Overall, 199 patients (14 %) received MT. CT on admission revealed that 54 patients (3.8 %) had CE within the subcapsular hematoma, 100 patients (7.1 %) had intraparenchymal CE, and 86 patients (6.1 %) had CE into the peritoneal cavity among the overall cohort. Multivariate analysis, adjusted for age, sex, age-adjusted shock index, injury severity, and laboratory and imaging factors, showed that intraparenchymal CE and CE into the peritoneal cavity were significantly associated with the need for MT (AOR: 2.50; 95 % CI, 1.50-4.16 and AOR: 4.98; 95 % CI, 2.75-9.02, respectively both p < 0.001). The latter significant association persisted in the subgroup of patients with spleen and liver injuries. CONCLUSION: Active CE into the free peritoneal cavity on admission CT was independently associated with a greater probability of receiving MT in pediatric BLSI. The CE grade may help clinicians plan blood transfusion strategies. LEVEL OF EVIDENCE: Level 4; Therapeutic/Care management.

Configurationally Nonselective Aquation of a Mononuclear Ru(II) Chloro Complex to Aquo Complex Isomers with Distinctive Aspects in Photoisomerization, Redox, and Catalytic Water Oxidation.

distal-[Ru(EtOtpy)(pynp)Cl]+ (d-EtO1Cl) (EtOtpy = 4'-ethoxy-2,2':6',2″-terpyridine, pynp = 2-(2-pyridyl)-1,8-naphthyridine), and distal/proximal-[Ru(EtOtpy)(pynp)OH2]2+ (d/p-EtO1H2O) complexes were newly synthesized to investigate the synergistic influence of the geometric configuration coupled with substituent introduction of an ethoxy (EtO) group on the physicochemical properties and reactions of the Ru(II) complexes. Configurationally nonselective aquation of d-EtO1Cl was uniquely observed to form d/p-EtO1H2O isomers in water, in contrast to configurationally selective aquation of distal-[Ru(tpy)(pynp)Cl]+ (d-1Cl, tpy = 2,2':6',2″-terpyridine) without the EtO group [Yamazaki, H. . J. Am. Chem. Soc. 2011, 133, 8846-8849].The kinetic profiles of the aquation reactions of d-EtO1Cl were well analyzed using a sequential reversible reaction model assuming the reversible interconversion between d/p-EtO1H2O isomers via d-EtO1Cl. The observed equilibrium constant (Kiso) of isomerization between p/d-EtO1H2O was calculated from the kinetic analysis as Kiso = 0.45, which is consistent with the final concentration ratio (1:0.43) of p/d-EtO1H2O generated in the aquation reaction of d-EtO1Cl. The irreversible photoisomerization from d-EtO1H2O to p-EtO1H2O was observed in water with an internal quantum yield (Φ) of 0.44% at 520 nm. Electrochemical measurements showed that d-EtO1H2O undergoes a 2-step oxidation reaction of 1H+-coupled 1e- processes of RuII-OH2/RuIII-OH and RuIII-OH/RuIV═O at pH 1.3-9.7, whereas p-EtO1H2O undergoes a 1-step oxidation reaction of a 2H+-coupled 2e- process of RuII-OH2/RuIV═O in the pH range of 1.8-11.5. Any redox potential of d/p-EtO1H2O isomers was decreased by the electro-donating EtO substitution, compared with distal/proximal-[Ru(tpy)(pynp)OH2]2+ (d/p-1H2O). The turnover frequency (kO2 = 1.7 × 10-2 s-1) of d-EtO1H2O for water oxidation catalysis is higher than that (3.5 × 10-4 s-1) of p-EtO1H2O by a factor of 48.6. The kO2 value (1.7 × 10-2 s-1) for d-EtO1H2O is 4.5-fold higher than those of d-1H2O (3.8 × 10-3 s-1). The higher kO2 value of d-EtO1H2O compared with d-1H2O could be explained by the fast oxidation rate from RuIV═O to RuV═O involved in the rate-determining step due to the electron-donating EtO group.

Early restricted oxygen therapy after resuscitation from cardiac arrest (ER-OXYTRAC): protocol for a stepped-wedge cluster randomised controlled trial.

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).

Temperature-Controlled Transformation of WO3 Nanowires into Active Facets-Exposed Hexagonal Prisms toward Efficient Visible-Light-Driven Water Oxidation.

A unique transformation of WO3 nanowires (NW-WO3) into hexagonal prisms (HP-WO3) was demonstrated by tuning the temperature of the (N2H4)WO3 precursor suspension prepared from tungstic acid and hydrazine as a structure-directing agent. The precursor preparation at 20 °C followed by calcination at 550 °C produced NW-WO3 nanocrystals (ca. <100 nm width, 3-5 µm length) with anisotropic growth of monoclinic WO3 crystals to (002) and (200) planes and a polycrystalline character with randomly oriented crystallites in the lateral face of nanowires. The precursor preparation at 45 °C followed by calcination at 550 °C produced HP-WO3 nanocrystals (ca. 500-1000 nm diameter) with preferentially exposed (002) and (020) facets on the top-flat and side-rectangle surfaces, respectively, of hexagonal prismatic WO3 nanocrystals with a single-crystalline character. The HP-WO3 electrode exhibited the superior photoelectrochemical (PEC) performance for visible-light-driven water oxidation to that for the NW-WO3 electrode; the incident photon-to-current conversion efficiency (IPCE) of 47% at 420 nm and 1.23 V vs RHE for HP-WO3 was 3.1-fold higher than 15% for the NW-WO3 electrode. PEC impedance data revealed that the bulk electron transport through the NW-WO3 layer with the unidirectional nanowire structure is more efficient than that through the HP-WO3 layer with the hexagonal prismatic structure. However, the water oxidation reaction at the surface for the HP-WO3 electrode is more efficient than the NW-WO3 electrode, contributing significantly to the superior PEC water oxidation performance observed for the HP-WO3 electrode. The efficient water oxidation reaction at the surface for the HP-WO3 electrode was explained by the high surface fraction of the active (002) facet with fewer grain boundaries and defects on the surface of HP-WO3 to suppress the electron-hole recombination at the surface.

Horse-Derived Ceramide Accentuates Glucosylceramide Synthase and Ceramide Synthase 3 by Activating PPARß/δ and/or PPARγ to Stimulate Ceramide Synthesis.

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), ß-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 PPARß/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 PPARß/δ and/or PPARγ to accelerate ceramide synthesis in the SC.

Staphylococcus aureus Biofilm Inhibiting Activity of Advanced Glycation Endproduct Crosslink Breaking and Glycation Inhibiting Compounds.

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.

Potential Therapeutic Approach of Melatonin against Omicron and Some Other Variants of SARS-CoV-2.

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.

Optimal target blood pressure in elderly with septic shock (OPTPRESS) trial: study protocol for a randomized controlled trial.

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.

Distinctive Aspects in Aquation, Proton-Coupled Redox, and Photoisomerization Reactions between Geometric Isomers of Mononuclear Ruthenium Complexes with a Large-π-Conjugated Tetradentate Ligand.

Geometric isomers of mononuclear ruthenium(II) complexes, distal-/proximal-[Ru(tpy)(dpda)Cl]+ (d-/p-RuCl, tpy = 2,2':6',2″-terpyridine, dpda = 2,7-bis(2-pyridyl)-1,8-diazaanthracene), were newly synthesized to comprehensively investigate the geometric and electronic structures and distinctive aspects in various reactions between isomers. The ultraviolet (UV)-visible absorption spectra of d-/p-RuCl isomers show intense bands for metal-to-ligand charge transfer (MLCT) at close wavelengths of 576 and 573 nm, respectively. However, time-dependent density functional theory (TD-DFT) calculations suggest that the MLCT transition of d-RuCl involves mainly single transitions to the π* orbital of the dpda ligand in contrast to mixing of the π* orbitals of the dpda and tpy ligands for p-RuCl. The aquation reaction (1.5 × 10-3 s-1) of p-RuCl to yield proximal-[Ru(tpy)(dpda)(OH2)]2+ (p-RuH2O) is faster than that (5.3 × 10-6 s-1) of d-RuCl in D2O/CD3OD (4:1 v/v) by three orders of magnitude, which resulted from the longer Ru-Cl bond by 0.017 Å and the distorted angle (100.2(3)°) of Cl-Ru-N (a nitrogen of dpda, being on a tpy plane) due to the steric repulsion between Cl and dpda for p-RuCl. Electrochemical measurements showed that d-RuH2O undergoes a 2-step oxidation reaction of 1H+-coupled 1e- processes of RuII-OH2/RuIII-OH and RuIII-OH/RuIV═O at pH 1-9, whereas p-RuH2O undergoes a 1-step oxidation reaction of a 2H+-coupled 2e- process of RuII-OH2/RuIV═O in the pH range of pH 1-10. The irreversible photoisomerization from d-RuH2O to p-RuH2O was observed in aqueous solution with an internal quantum yield (Φ) of 5.4 × 10-3% at 520 nm, which is lower compared with Φ = 1.1-2.1% of mononuclear Ru(II) aquo complexes with similar bidentate ligands instead of dpda by three orders of magnitude. This is possibly ascribed to the faster nonradiative decay rate from the excited 3MLCT state to the ground state for d-RuH2O due to the lower π* level of dpda ligands according to the energy-gap law: the rate decreases exponentially with the increasing energy gap.

Effect of facial application of essence containing royal jelly extract on stratum corneum moisture content: A placebo-controlled, double-blind, parallel-group study.

OBJECTIVES: To evaluate the moisturizing function and other effects of royal jelly extract on the skin. The effects of applying an essence containing royal jelly extract on the skin of healthy Japanese males and females were examined. METHODS: Thirty-five healthy Japanese men and women who were aware of their skin dryness applied an essence containing royal jelly extract or placebo for 4 weeks using the split-face method in a placebo-controlled, double-blind, parallel comparative study. The stratum corneum water content, transepidermal water evaporation, pigmentation, pores, and redness were evaluated. RESULTS: The stratum corneum water content significantly increased by the application of essence containing royal jelly extract to the cheeks for 4 weeks compared with placebo. CONCLUSION: The application of an essence containing royal jelly extract significantly improved the moisture content of the stratum corneum of the cheeks, confirming the improvement in the moisturizing function of the royal jelly extract. Furthermore, no adverse events were observed at the application site during the application period, and the test products and royal jelly extract contained in the test product were considered highly safe.

Early intubation and decreased in-hospital mortality in patients with coronavirus disease 2019.

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 < 0.001). The beneficial effects of early intubation were observed regardless of age and severity of hypoxemia at time of intubation; however, early intubation was associated with lower in-hospital mortality only among patients who were intubated later than 2 days after admission. CONCLUSIONS: Early intubation in the setting of ≤ 6 L/min of oxygen usage was associated with decreased in-hospital mortality among patients with COVID-19 who required intubation. Trial Registration None.

Highly Efficient and Durable Electrocatalysis by a Molecular Catalyst with Long Alkoxyl Chains Immobilized on a Carbon Electrode for Water Oxidation.

A dinuclear Ru complex, proximal,proximal-[Ru2L(C8Otpy)2(OH)(OH2)]3+ (C8Otpy = 4'-octyloxy-2,2'; 6',2″-terpyridine) (1) with long alkoxyl chains, was synthesized to be immobilized on a carbon paper (CP) electrode via hydrophobic interactions between the long alkoxyl chains and the CP surface. The 1/CP electrode demonstrated efficient electrocatalytic water oxidation with a low overpotential (ηonset) of 0.26 V (based on the onset potential for water oxidation) in an aqueous medium at pH 7.0, which is compared advantageously with those of hitherto-reported molecular anodes for water oxidation. The active species of RuIIIRuIII(µ-OO) with a µ-OO bridge was involved in water oxidation at 0.95 V versus Ag/AgCl. As the applied potential increased to 1.40 V, water oxidation was promoted by participation of the more active species of RuIIIRuIV(µ-OO), and very durable electrocatalysis was gained for more than 35 h without elution of 1 into the electrolyte solution. The introduced long alkoxyl chains act as a dual role of the linker of 1 on the CP surface and decrease the η value. Theoretical investigation provides insights into the O-O bond formation mechanism and the activity difference between RuIIIRuIII(µ-OO) and RuIIIRuIV(µ-OO) for electrocatalytic water oxidation.

Life-saving case of cardiopulmonary arrest by secondary aortoenteric fistula formed in the anastomotic site between the inferior mesenteric artery and aortic graft.

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.

Serial Passaging of RAW 264.7 Cells Modulates Intracellular AGE Formation and Downregulates RANKL-Induced In Vitro Osteoclastogenesis.

The passage number of cells refers to the number of subculturing processes that the cells have undergone. The effect of passage number on morphological and phenotypical characteristics of cells is of great importance. Advanced glycation end products have also been associated with cell functionality and characteristics. Murine monocyte RAW 264.7 cells differentiate into osteoclasts upon receptor activation caused by nuclear factor-kappa-Β ligand (RANKL) treatment. This study aims to identify the role of passage number on intracellular advanced glycation end products (AGEs) formation and osteoclastogenic differentiation of RAW 264.7 cells. Western blotting was performed to check intracellular AGE formation along with fluorometric analysis using a microplate reader. Tartrate-resistant acid phosphatase (TRAP) staining was performed to check osteoclastogenic differentiation, and qPCR was realized to check the responsible mRNA expression. Immunofluorescence was used to check the morphological changes. Intracellular AGE formation was increased with passaging, and the higher passage number inhibited multinucleated osteoclastogenic differentiation. Osteoclastogenic gene expression also showed a reducing trend in higher passages, along with a significant reduction in F-actin ring size and number. Lower passages should be used to avoid the effects of cell subculturing in in vitro osteoclastogenesis study using RAW 264.7 cells.

Mechanism of H+ dissociation-induced O-O bond formation via intramolecular coupling of vicinal hydroxo ligands on low-valent Ru(III) centers.

The understanding of O-O bond formation is of great importance for revealing the mechanism of water oxidation in photosynthesis and for developing efficient catalysts for water oxidation in artificial photosynthesis. The chemical oxidation of the RuII2(OH)(OH2) core with the vicinal OH and OH2 ligands was spectroscopically and theoretically investigated to provide a mechanistic insight into the O-O bond formation in the core. We demonstrate O-O bond formation at the low-valent RuIII2(OH) core with the vicinal OH ligands to form the RuII2(µ-OOH) core with a µ-OOH bridge. The O-O bond formation is induced by deprotonation of one of the OH ligands of RuIII2(OH)2 via intramolecular coupling of the OH and deprotonated O- ligands, conjugated with two-electron transfer from two RuIII centers to their ligands. The intersystem crossing between singlet and triple states of RuII2(µ-OOH) is easily switched by exchange of H+ between the µ-OOH bridge and the auxiliary backbone ligand.

Three millimeter needlescopic splenectomy using three-port technique: report of three cases.

We report our experience with needlescopic splenectomy (NS) for the surgical treatment of idiopathic thrombocytopenic purpura using a 3-mm needlescope with three ports. One patient was male and two were females, and their mean age was 58 years. The patient was placed in the right lateral decubitus position. The first 12-mm port was introduced through the lateral margin of the left rectus abdominis muscle, and the other two 3-mm ports were inserted in the left upper quadrant. NS was performed by a standard technique under the observation of 3.3-mm needlescope. The surgical procedure was successfully completed in all the patients. The mean duration of surgery, intra-operative bleeding volume and post-operative hospital stay were 176 min, 70 ml and 4.7 days, respectively. There were no particular peri-operative complications in spite of dense adhesions or simultaneous laparoscopic procedures. Our method is safe and feasible with low morbidity and without impairing cosmetic benefits.

Facile Fabrication of a Highly Crystalline and Well-Interconnected Hematite Nanoparticle Photoanode for Efficient Visible-Light-Driven Water Oxidation.

Facile and scalable fabrication of α-Fe2O3 photoanodes using a precursor solution containing FeIII ions and 1-ethylimidazole (EIm) in methanol was demonstrated to afford a rigidly adhered α-Fe2O3 film with a controllable thickness on a fluorine-doped tin oxide (FTO) substrate. EIm ligation to FeIII ions in the precursor solution brought about high crystallinity of three-dimensionally well-interconnected nanoparticles of α-Fe2O3 upon sintering. This is responsible for the 13.6 times higher photocurrent density (at 1.23 V vs reference hydrogen electrode (RHE)) for photoelectrochemical (PEC) water oxidation on the α-Fe2O3 (w-α-Fe2O3) photoanode prepared with EIm compared with that (w/o-α-Fe2O3) prepared without EIm. The w-α-Fe2O3 photoanode provided the highest charge separation efficiency (ηsep) value of 27% among the state-of-the-art pristine α-Fe2O3 photoanodes, providing incident photon-to-current conversion efficiency (IPCE) of 13% at 420 nm and 1.23 V vs RHE. The superior ηsep for the w-α-Fe2O3 photoanode is attributed to the decreased recombination of the photogenerated charge carriers at the grain boundary between nanoparticles, in addition to the higher number of the catalytically active sites and the efficient bulk charge transport in the film, compared with w/o-α-Fe2O3.

Vagus nerve stimulation modulates arachidonic acid production in the mesenteric lymph following intestinal ischemia-reperfusion injury.

BACKGROUND: Inflammatory lipid mediators in mesenteric lymph (ML), including arachidonic acid (AA), are considered to play an important role in the pathogenesis of multiple-organ dysfunction after hemorrhagic shock. A previous study suggested that vagus nerve stimulation (VNS) could relieve shock-induced gut injury and abrogate ML toxicity, resulting in the prevention of multiple-organ dysfunction. However, the detailed mechanism of VNS in lymph toxicity remains unclear. The study aimed to investigate the relationship between VNS and inflammatory lipid mediators in ML. METHODS: Male Sprague-Dawley rats underwent laparotomy and superior mesenteric artery obstruction (SMAO) for 60 minutes to induce intestinal ischemia followed by reperfusion and observation. The ML duct was cannulated, and ML samples were obtained both before and after SMAO. The distal ileum was removed at the end of the observation period. In one group of animals, VNS was performed from 10 minutes before 10 minutes after SMAO (5 V, 0.5 Hz). Liquid chromatography-electrospray ionization-tandem mass spectrometry analysis of AA was performed for each ML sample. The biological activity of ML was examined using a monocyte nuclear factor κ-light-chain-enhancer of activated B cells activation assay. Western blotting of phospholipase A2 group IIA (PLA2-IIA) was also performed for ML and ileum samples. RESULTS: Vagus nerve stimulation relieved the SMAO-induced histological gut injury. The concentration of AA and level of nuclear factor κ-light-chain-enhancer of activated B cells activation in ML increased significantly after SMAO, whereas VNS prevented these responses. Western blotting showed PLA2-IIA expression in the ML and ileum after SMAO; however, the appearance of PLA2-IIA band was remarkably decreased in the samples from VNS-treated animals. CONCLUSION: The results suggested that VNS could relieve gut injury induced by SMAO and decrease the production of AA in ML by altering PLA2-IIA expression in the gut and ML.

Evaluation of bleeding control course for health-care providers in Japan.

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 < 0.05). CONCLUSION: The BCon course and tourniquets were well-received by all types of HCPs in Japan.