Non-linear association between the time required to reaching temperature targets and the neurological outcome in patients undergoing targeted temperature management after out-of-hospital cardiac arrest: Observational multicentre cohort study.

Purpose: We evaluated associations between outcomes and time to achieving temperature targets during targeted temperature management of out-of-hospital cardiac arrest. Methods: Using Comprehensive Registry of Intensive Care for out-of-hospital cardiac arrest Survival (CRITICAL) study, we enrolled all patients transported to participating hospitals from 1 July 2012 through 31 December 2017 aged ≥ 18 years with out-of-hospital cardiac arrest of cardiac aetiology and who received targeted temperature management in Osaka, Japan. Primary outcome was Cerebral Performance Category scale of 1 or 2 one month after cardiac arrest, designated as "one-month favourable neurological outcome". Non-linear multivariable logistic regression analyses assessed the primary outcome based on time to reaching temperature targets. In patients subdivided into quintiles based on time to achieving temperature targets, multivariable logistic regression calculated adjusted odds ratios and 95% confidence intervals. Results: We analysed 473 patients. In non-linear multivariable logistic regression analysis, p value for non-linearity was < 0.01. In the first quintile (< 26.7 minutes), second quintile (26.8-89.9 minutes), third quintile (90.0-175.1 minutes), fourth quintile (175.2-352.1 minutes), and fifth quintile (≥ 352.2 minutes), one-month favourable neurological outcome was 32.6% (31/95), 40.0% (36/90), 53.5% (53/99), 57.4% (54/94), and 37.9% (36/95), respectively. Adjusted odds ratios with 95% confidence intervals for one-month favourable neurological outcome in the first, second, third, and fifth quintiles compared with the fourth quintile were 0.38 (0.20 to 0.72), 0.43 (0.23 to 0.81), 0.77 (0.41 to 1.44), and 0.46 (0.25 to 0.87), respectively. Conclusion: Non-linear multivariable logistic regression analysis could clearly describe the association between neurological outcome in patients with out-of-hospital cardiac arrest and the time from the introduction of targeted temperature management to reaching the temperature targets.

Fast-Response and Low-Power Self-Heating Gas Sensor Using Metal/Metal Oxide/Metal (MMOM) Structured Nanowires.

With the escalating global awareness of air quality management, the need for continuous and reliable monitoring of toxic gases by using low-power operating systems has become increasingly important. One of which, semiconductor metal oxide gas sensors have received great attention due to their high/fast response and simple working mechanism. More specifically, self-heating metal oxide gas sensors, wherein direct thermal activation in the sensing material, have been sought for their low power-consuming characteristics. However, previous works have neglected to address the temperature distribution within the sensing material, resulting in inefficient gas response and prolonged response/recovery times, particularly due to the low-temperature regions. Here, we present a unique metal/metal oxide/metal (MMOM) nanowire architecture that conductively confines heat to the sensing material, achieving high uniformity in the temperature distribution. The proposed structure enables uniform thermal activation within the sensing material, allowing the sensor to efficiently react with the toxic gas. As a result, the proposed MMOM gas sensor showed significantly enhanced gas response (from 6.7 to 20.1% at 30 ppm), response time (from 195 to 17 s at 30 ppm), and limit of detection (∼1 ppm) when compared to those of conventional single-material structures upon exposure to carbon monoxide. Furthermore, the proposed work demonstrated low power consumption (2.36 mW) and high thermal durability (1500 on/off cycles), demonstrating its potential for practical applications in reliable and low-power operating gas sensor systems. These results propose a new paradigm for power-efficient and robust self-heating metal oxide gas sensors with potential implications for other fields requiring thermal engineering.

Changes in structural plasticity of hippocampal neurons in an animal model of multiple sclerosis.

Structural plasticity is critical for the functional diversity of neurons in the brain. Experimental autoimmune encephalomyelitis (EAE) is the most commonly used model for multiple sclerosis (MS), successfully mimicking its key pathological features (inflammation, demyelination, axonal loss, and gliosis) and clinical symptoms (motor and non-motor dysfunctions). Recent studies have demonstrated the importance of synaptic plasticity in EAE pathogenesis. In the present study, we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase (11 days post-immunization, DPI) and chronic phase (28 DPI). EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic phases. Dendritic complexity was largely affected in the cornu ammonis 1 (CA1) and CA3 apical and dentate gyrus (DG) subregions of the hippocampus during the chronic phase, while this effect was only noted in the CA1 apical subregion in the early phase. Moreover, dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE, but only reduced in the DG subregion during the chronic phase. Furthermore, mRNA levels of proinflammatory cytokines ( Il1ß, Tnfα, and Ifnγ) and glial cell markers ( Gfap and Cd68) were significantly increased, whereas the expression of activity-regulated cytoskeleton-associated protein (ARC) was reduced during the chronic phase. Similarly, exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC expression. Primary cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase (ERK) phosphorylation upon treatment with proinflammatory cytokines. Collectively, these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus, possibly through the ERK-ARC pathway, indicating that this alteration may be associated with hippocampal dysfunctions in EAE.

The Relative Contribution of Facial and Body Information to the Perception of Cuteness.

Faces and bodies both provide cues to age and cuteness, but little work has explored their interaction in cuteness perception. This study examines the interplay of facial and bodily cues in the perception of cuteness, particularly when these cues convey conflicting age information. Participants rated the cuteness of face-body composites that combined either a child or adult face with an age-congruent or incongruent body alongside manipulations of the head-to-body height ratio (HBR). The findings from two experiments indicated that child-like facial features enhanced the perceived cuteness of adult bodies, while child-like bodily features generally had negative impacts. Furthermore, the results showed that an increased head size significantly boosted the perceived cuteness for child faces more than for adult faces. Lastly, the influence of the HBR was more pronounced when the outline of a body's silhouette was the only available information compared to when detailed facial and bodily features were presented. This study suggests that body proportion information, derived from the body's outline, and facial and bodily features, derived from the interior surface, are integrated to form a unitary representation of a whole person in cuteness perception. Our findings highlight the dominance of facial features over bodily information in cuteness perception, with facial attributes serving as key references for evaluating face-body relationships and body proportions. This research offers significant insights into social cognition and character design, particularly in how people perceive entities with mixed features of different social categories, underlining the importance of congruency in perceptual elements.

Use of biosilica to improve loading and delivery of bone morphogenic protein 2.

The clinical utility of bone morphogenetic protein 2 (BMP2) is limited because of the poor attraction between BMP2 and carriers, resulting in low loading efficiency and initial burst release. Here, the high binding affinity of BMP2 to the biosilica surface was utilized to overcome this limitation. Atomic force microscopy revealed that BMP2 bound nearly 8- and 2-fold more strongly to biosilica-coated hydroxyapatite than to uncoated and plain silica-coated hydroxyapatite, respectively. To achieve controlled release, collagen was introduced between the silica layers on hydroxyapatite, which was optimized by adjusting the collagen concentration and number of layers. The optimal biosilica/collagen formulation induced sustained BMP2 release without compromising loading efficiency. BMP2 combined with the mentioned formulation led to an increase in osteogenesis, as compared to the combination of BMP2 with either biosilica-coated or non-coated hydroxyapatite in vitro. In rat calvarial defect models, the biosilica/collagen-coated hydroxyapatite with 1 µg BMP2 showed 26 % more bone regeneration than the same dose of BMP2-loaded hydroxyapatite and 10.6 % more than hydroxyapatite with 2.5-fold dose of BMP2. Using BMP2 affinity carriers coated with biosilica/collagen allows for more efficacious in situ loading and delivery of BMP2, making them suitable for the clinical application of growth factors through a soaking method.

Ultrathin Serpentine Insulation Layer Architecture for Ultralow Power Gas Sensor.

Toxic gases have surreptitiously influenced the health and environment of contemporary society with their odorless/colorless characteristics. As a result, a pressing need for reliable and portable gas-sensing devices has continuously increased. However, with their negligence to efficiently microstructure their bulky supportive layer on which the sensing and heating materials are located, previous semiconductor metal-oxide gas sensors have been unable to fully enhance their power efficiency, a critical factor in power-stringent portable devices. Herein, an ultrathin insulation layer with a unique serpentine architecture is proposed for the development of a power-efficient gas sensor, consuming only 2.3 mW with an operating temperature of 300 °C (≈6% of the leading commercial product). Utilizing a mechanically robust serpentine design, this work presents a fully suspended standalone device with a supportive layer thickness of only ≈50 nm. The developed gas sensor shows excellent mechanical durability, operating over 10 000 on/off cycles and ≈2 years of life expectancy under continuous operation. The gas sensor detected carbon monoxide concentrations from 30 to 1 ppm with an average response time of ≈15 s and distinguishable sensitivity to 1 ppm (ΔR/R0 = 5%). The mass-producible fabrication and heating efficiency presented here provide an exemplary platform for diverse power-efficient-related devices.

Ultrafast (∼0.6 s), Robust, and Highly Linear Hydrogen Detection up to 10% Using Fully Suspended Pure Pd Nanowire.

The high explosiveness of hydrogen gas in the air necessitates prompt detection in settings where hydrogen is used. For this reason, hydrogen sensors are required to offer rapid detection and possess superior sensing characteristics in terms of measurement range, linearity, selectivity, lifetime, and environment insensitivity according to the publicized protocol. However, previous approaches have only partially achieved the standardized requirements and have been limited in their capability to develop reliable materials for spatially accessible systems. Here, an electrical hydrogen sensor with an ultrafast response (∼0.6 s) satisfying all demands for hydrogen detection is demonstrated. Tailoring structural engineering based on the reaction kinetics of hydrogen and palladium, an optimized heating architecture that thermally activates fully suspended palladium (Pd) nanowires at a uniform temperature is designed. The developed Pd nanostructure, at a designated temperature distribution, rapidly reacts with hydrogen, enabling a hysteresis-free response from 0.1% to 10% and durable characteristics in mechanical shock and repetitive operation (>10,000 cycles). Moreover, the device selectively detects hydrogen without performance degradation in humid or carbon-based interfering gas circumstances. Finally, to verify spatial accessibility, the wireless hydrogen detection system has been demonstrated, detecting and reporting hydrogen leakage in real-time within just 1 s.

In-hospital extracorporeal cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest: an analysis by time-dependent propensity score matching using a nationwide database in Japan.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has been proposed as a rescue therapy for patients with refractory cardiac arrest. This study aimed to evaluate the association between ECPR and clinical outcomes among patients with out-of-hospital cardiac arrest (OHCA) using risk-set matching with a time-dependent propensity score. METHODS: This was a secondary analysis of the JAAM-OHCA registry data, a nationwide multicenter prospective study of patients with OHCA, from June 2014 and December 2019, that included adults (≥ 18 years) with OHCA. Initial cardiac rhythm was classified as shockable and non-shockable. Patients who received ECPR were sequentially matched with the control, within the same time (minutes) based on time-dependent propensity scores calculated from potential confounders. The odds ratios with 95% confidence intervals (CI) for 30-day survival and 30-day favorable neurological outcomes were estimated for ECPR cases using a conditional logistic model. RESULTS: Of 57,754 patients in the JAAM-OHCA registry, we selected 1826 patients with an initial shockable rhythm (treated with ECPR, n = 913 and control, n = 913) and a cohort of 740 patients with an initial non-shockable rhythm (treated with ECPR, n = 370 and control, n = 370). In these matched cohorts, the odds ratio for 30-day survival in the ECPR group was 1.76 [95%CI 1.38-2.25] for shockable rhythm and 5.37 [95%CI 2.53-11.43] for non-shockable rhythm, compared to controls. For favorable neurological outcomes, the odds ratio in the ECPR group was 1.11 [95%CI 0.82-1.49] for shockable rhythm and 4.25 [95%CI 1.43-12.63] for non-shockable rhythm, compared to controls. CONCLUSION: ECPR was associated with increased 30-day survival in patients with OHCA with initial shockable and even non-shockable rhythms. Further research is warranted to investigate the reproducibility of the results and who is the best candidate for ECPR.

Immunohistochemical analysis of extracellular signal-regulated kinase expression in mature and immature bulls' testes and epididymides.

Extracellular signal-regulated kinase (ERK) has been implicated in mammalian testicular and epididymal development. This study aimed to investigate ERK expression in the immature and mature testes and epididymides of bulls. We evaluated ERK expression using immunoblot analysis and immunohistochemistry. Immunoblot analysis revealed that immature bull testes and epididymides had higher phosphorylated ERK (pERK) expression than mature bull testes and epididymides. pERK immunoreactivity was higher in immature epididymides than in immature testes. pERK was localised mostly in spermatogonia, undifferentiated sustentacular (Sertoli) cells, and interstitial (Leydig) cells in immature testes, as well as in some spermatocytes and spermatids in mature testes. In immature epididymides, the body and tail had higher pERK expression than the head, whereas pERK was broadly distributed throughout the stereocilia, basal cells, and connective tissues. pERK distribution in the head of mature epididymides was similar to that in immature epididymides, whereas few connective tissue cells were expressed in the body and tail of mature epididymides. Collectively, these results suggest that ERK is expressed in the testis and epididymis of immature and mature bulls with varying intensities, and the role of ERK in male reproductive organs may include the specific function of its development.

Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their vulnerability to protease degradation and toxicity towards mammalian cells has hindered their clinical application. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs applicable to effective drug-device combination products. The KR12 antimicrobial peptide was chosen, and in order to further enhance its delivery and efficacy the human immunodeficiency virus TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica particles with self-entrapped CPP-KR12 peptide using biomimetic silica precipitability because of its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was observed at a slightly delivered rate, with improved stability against trypsin treatment and a reduction in cytotoxicity compared to CPP-KR12. Finally, the antimicrobial potential of the CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated. CPP-KR12 is coated in the form of submicron-sized particles on the surface of the BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug-device combination product for tissue regeneration.

Gemigliptin, a DPP4 inhibitor, ameliorates nonalcoholic steatohepatitis through AMP-activated protein kinase-independent and ULK1-mediated autophagy.

OBJECTIVE: Abnormal autophagic function and activated inflammasomes are typical features in the liver of patients with non-alcoholic steatohepatitis (NASH). Here, we explored whether gemigliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor for treatment of type 2 diabetes, can induce autophagy and regulate inflammasome activation as a potential NASH treatment independent of its anti-diabetic effect. METHODS: Expression analysis was performed using human liver samples obtained from 18 subjects who underwent hepatectomy. We explored the function and mechanism of gemigliptin using a methionine- and choline-deficient diet (MCD)-induced NASH mouse model and HepG2 cells cultured in MCD-mimicking medium. RESULTS: Autophagy was suppressed by marked decreases in the expression of ULK1 and LC3II/LC3I ratio in human NAFLD/NASH patients, a NASH mouse model, and HepG2 cells cultured with MCD-mimicking media. Surprisingly, we found that the expression of p-AMPK decreased in liver tissues from patients with steatosis but was restored in NASH patients. The expression of p-AMPK in the NASH mouse model was similar to that of the control group. Hence, these results indicate that autophagy was reduced in NASH via an AMPK-independent pathway. However, gemigliptin treatment attenuated lipid accumulation, inflammation, and fibrosis in the liver of MCD diet-fed mice with restoration of ULK1 expression and autophagy induction. In vitro, gemigliptin alleviated inflammasome activation through induction of ULK1-dependent autophagy. Furthermore, gemigliptin treatment upregulated ULK1 expression and activated AMPK even after siRNA-mediated knockdown of AMPKα1/2 and ULK1, respectively. CONCLUSIONS: Collectively, these results suggest that gemigliptin ameliorated NASH via AMPK-independent, ULK1-mediated effects on autophagy.

Intra-Aortic Balloon Pump among Shockable Out-of-Hospital Cardiac Arrest Patients: A Propensity-Weighted Analysis in a Multicenter, Nationwide Observational Study in Japan (The JAAM-OHCA Registry).

BACKGROUND: The effectiveness of IABP for shockable out-of-hospital cardiac arrest (OHCA) has not been extensively investigated. This study aimed to investigate whether the use of an intra-aortic balloon pump (IABP) for non-traumatic shockable OHCA patients was associated with favorable neurological outcomes. METHODS: From the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry, a nationwide multicenter prospective registry, we enrolled adult patients with non-traumatic and shockable OHCA for whom resuscitation was attempted, and who were transported to participating hospitals between 2014 and 2019. The primary outcome was 1-month survival with favorable neurological outcomes after OHCA. After adopting the propensity score (PS) inverse probability of weighting (IPW), we evaluated the association between IABP and favorable neurological outcomes. RESULTS: Of 57,754 patients in the database, we included a total of 2738 adult non-traumatic shockable patients. In the original cohort, the primary outcome was lower in the IABP group (OR with 95% confidence intervals (CIs)), 0.57 (0.48-0.68), whereas, in the IPW cohort, it was not different between patients with and without IABP (OR, 1.18; 95% CI, 0.91-1.53). CONCLUSION: In adult patients with non-traumatic shockable OHCA, IABP use was not associated with 1-month survival with favorable neurological outcomes.

Toxicity of a 90-day repeated oral dose of a collagen peptide derived from skate (Raja kenojei) skin: a rat model study.

Collagen peptides are widely employed as therapeutic materials due to their numerous beneficial properties, including for the following uses: antiaging, antioxidant applications, antibacterial applications, wound healing, tissue engineering, medication delivery, and cosmetics. Although collagen peptides are useful in these applications, to our knowledge, few published studies have been undertaken on their repeated-dose toxicity. We evaluated the possible subchronic toxicity of a collagen peptide derived from skate (Raja kenojei) skin (CPSS) in Sprague-Dawley rats by administering repeated oral doses over 90 days. Rats of both sexes were assigned randomly to one of four experimental groups, respectively receiving 0, 500, 1000, or 2000 mg/kg/day of CPSS. At all doses tested, repeated oral CPSS administration had no treatment-related adverse effects in terms of clinical signs, body weight, food consumption, detailed clinical observation, sensory reactivity, functional assessment, urinalysis, ophthalmic examination, gross pathology, hematology, serum biochemistry, hormone analysis, organ weight, and histopathology. Even though there were some alterations in hematologic parameters, serum biochemistry parameters, organ weight, and histopathological findings, these did not follow a dose-response pattern and were within historical limits for control rats. The oral no-observed-adverse-effect level (NOAEL) of the CPSS was 2000 mg/kg/day for both male and female rats in the applied experimental circumstances, and no target organs were identified.

Competition Between Object Topology and Surface Features in Children's Extension of Novel Nouns.

Objects' topological properties play a central role in object perception, superseding objects' surface features in object representation and tracking from early in development. We asked about the role of objects' topological properties in children's generalization of novel labels to objects. We adapted the classic name generalization task of Landau et al. (1988, 1992). In three experiments, we showed children (n = 151; 3-8-year-olds) a novel object (the standard) and gave the object a novel label. We then showed children three potential target objects and asked children which of the objects shared the same label as the standard. In Experiment 1, the standard object either did or did not contain a hole, and we asked whether children would extend the standard's label to a target object that shared either metric shape or topology with the standard. Experiment 2 served as a control condition for Experiment 1. In Experiment 3, we pitted topology against another surface feature, color. We found that objects' topology competed with objects' surface features (both shape and color) in children's extension of labels to novel objects. We discuss possible implications for our understanding of the inductive potential of objects' topologies for making inferences about objects' categories across early development.

Modified deep-plane facelift and lower midface lifting using deep fat compartment mobilization and zygomaticus major muscle plication.

BACKGROUND: Most facelift techniques greatly improve the lower face; however, techniques for lifting the midface are limited and difficult. Original deep plane face lift is a way to lift the SMAS and skin as a compound unit. Though it minimizes SMAS tear during dissection, damage to the vascular system and incidence of skin necrosis and can be easily used in secondary cases, it does not adequately improve nasolabial fold. We perform a modified and enhanced deep plane facelift to improve the midface. Herein, we explain the effects and procedures of the method. METHODS: This retrospective study included patients (n=632) on whom deep-plane facelift (DPF group, n=299) and modified deep-plane facelift (M-DPF group, n=333) was performed by a single surgeon from January 2014 to January 2017 and February 2017 to December 2020, respectively, at a local clinic. The degree of improvement in wrinkles in the patients' nasolabial fold was assessed using a 5-grade wrinkle severity rating scale (WSRS). RESULTS: Preoperative WSRS was 2.95 ± 0.89 in the DPF group and 2.89 ± 0.92 in the M-DPF group. There was no significant difference in preoperative WSRS between the two groups (p=0.058). Postoperative WSRS was 1.81 ± 0.68 in the DPF group, which was significantly greater than the 1.65 ± 0.66 found in the M-DPF group. CONCLUSIONS: This method developed by us that combines deep-plane facelift with deep fat compartment mobilization and zygomaticus major muscle plication is safe and directly improves the nasolabial fold and promotes a smiling expression for rejuvenation effects.

Diagnostic test accuracy of life-threatening electrocardiographic findings (ST-elevation myocardial infarction equivalents) for acute coronary syndrome after out-of-hospital cardiac arrest without ST-segment elevation.

AIM: Life-threatening electrocardiographic (ECG) findings aid in the diagnosis of acute coronary syndrome (ACS), which has not been well-evaluated in patients with out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate the diagnostic test accuracy (DTA) of ST-elevation myocardial infarction (STEMI) equivalents following the return of spontaneous circulation (ROSC) in patients with OHCA to identify patients with ACS. METHODS: Using the database of the Comprehensive Registry of In-Hospital Intensive Care for OHCA Survival study from 2012 to 2017, patients aged ≥18 years with non-traumatic OHCA and ventricular fibrillation or pulseless ventricular tachycardia on the arrival of emergency medical service personnel or arrival at the emergency department, who achieved ROSC, were included. Patients without ST-segment elevation or complete left bundle branch block on ECG and those who did not undergo ECG or coronary angiography, were excluded from the study. We evaluated the DTA of STEMI equivalents for the diagnosis of ACS: isolated T-wave inversion, ST-segment depression, Wellens' signs, and ST-segment elevation in lead aVR. RESULTS: Isolated T-wave inversion and Wellens' signs had high specificity for ACS with 0.95 (95% confidence interval [CI], 0.87-0.99) and 0.92 (95% CI, 0.82-0.97), respectively, but their positive likelihood ratios were low, with a wide range of 95% CI: 1.89 (95% CI, 0.51-7.02) and 0.81 (95% CI, 0.25-2.68), respectively. CONCLUSION: The DTA of STEMI equivalents for the diagnosis of ACS was low among patients with OHCA. Further investigation considering the measurement timing of the ECG after ROSC is required.

BMP2-Mediated Silica Deposition: An Effective Strategy for Bone Mineralization.

The combined use of an osteogenic factor, such as bone morphogenetic protein 2 (BMP2), with a bone scaffold was quite functional for the reconstruction of bone defects. Although many studies using BMP2 have been done, there is still a need to develop an efficient way to apply BMP2 in the bone scaffold. Here, we reported an interesting fact that BMP2 has a silica deposition ability in the presence of silicic acid and proposed that such an ability of BMP2 can effectively immobilize and transport itself by a kind of coprecipitation of BMP2 with a silica matrix. The presence of BMP2 in the resulting silica was proved by SEM and EDS and was visualized by FITC-labeled BMP2. The delivery efficacy of BMP2 of silica-entrapped BMP2 on osteoblast differentiation and mineralization using MC3T3 E1 preosteoblast cells was evaluated in vitro. The coprecipitated BMP2 with silica exhibited osteogenesis at a low concentration that was insufficient to give an osteoinductive signal as the free form. Expectedly, the silica-entrapped BMP2 exhibited thermal stability over free BMP2. When applied to bone graft substitution, e.g., hydroxyapatite granules (HA), silica-entrapped BMP 2 laden HA (BMP2@Si/HA) showed sustained BMP2 release, whereas free BMP2 adsorbed HA by a simple dipping method (BMP2/HA) displayed a burst release of BMP2 at an initial time. In the rat critical-size calvarial defect model, BMP2@Si/HA showed better bone regeneration than BMP2/HA by about 10%. The BMP2/silica hybrid deposited on a carrier surface via BMP2-mediated silica precipitation demonstrated an increase in the loading efficiency, a decrease in the burst release of BMP2, and an increase in bone regeneration. Taken together, the coprecipitated BMP2 with a silica matrix has the advantages of not only being able to immobilize BMP2 efficiently without compromising its function but also serving as a stable carrier for BMP2 delivery.

Association between blood urea nitrogen to creatinine ratio and neurologically favourable outcomes in out-of-hospital cardiac arrest in adults: A multicentre cohort study.

BACKGROUND: We aimed to investigate the association between blood urea nitrogen to creatinine ratio (BCR) and survival with favourable neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA). METHODS: This prospective, multicentre, observational study conducted in Osaka, Japan enrolled consecutive OHCA patients transported to 16 participating institutions from 2012 through 2019. We included adult patients with non-traumatic OHCA who achieved a return of spontaneous circulation and whose blood urea nitrogen and creatinine levels on hospital arrival were available. Based on BCR values, they were divided into: 'low BCR' (BCR <10), 'normal BCR' (10 ≤ BCR < 20), 'high BCR' (20 ≤ BCR < 30), and 'very high BCR' (BCR ≥ 30). We evaluated the association between BCR values and neurologically favourable outcomes, defined as cerebral performance category score of 1 or 2 at one month after OHCA. RESULTS: Among 4415 eligible patients, the 'normal BCR' group had the highest favourable neurological outcome [19.4 % (461/2372)], followed by 'high BCR' [12.5 % (141/1127)], 'low BCR' [11.2 % (50/445)], and 'very high BCR' groups [6.6 % (31/471)]. In the multivariable analysis, adjusted odds ratios for 'low BCR', 'high BCR', and 'very high BCR' compared with 'normal BCR' for favourable neurological outcomes were 0.58 [95 % confidence interval (CI 0.37-0.91)], 0.70 (95 % CI 0.49-0.99), and 0.40 (95 % CI 0.21-0.76), respectively. Cubic spline analysis indicated that the association between BCR and favourable neurological outcomes was non-linear (p for non-linearity = 0.003). In subgroup analysis, there was an interaction between the aetiology of arrest and BCR in neurological outcome (p for interaction <0.001); favourable neurological outcome of cardiogenic OHCA patients was lower when the BCR was higher or lower, but not in non-cardiogenic OHCA patients. CONCLUSIONS: Both higher and lower BCR were associated with poor neurological outcomes compared to normal BCR, especially in cardiogenic OHCA patients.

External validation of the TiPS65 score for predicting good neurological outcomes in patients with out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation.

AIM: Estimating prognosis of patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) is essential for selecting candidates. The TiPS65 score can predict neurological outcomes of patients with out-of-hospital cardiac arrest (OHCA) treated with ECPR. We aimed to perform an external validation of this score. METHODS: Data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry, a multicentred, nationwide, prospectively registered database, were analysed. All adult patients with OHCA and shockable rhythm and treated with ECPR between January 2018 to December 2019 were included. In the TiPS65 score, age, call-to-hospital arrival time, initial cardiac rhythm at hospital arrival, and initial pH value were used as predictors. The primary outcome was 30-day survival with favourable neurological outcomes (Cerebral Performance Category 1 or 2). Discrimination, using the C-statistic, and predictive performances of each score, such as sensitivity and specificity, were investigated. RESULTS: Of 590 included patients (517 [81.6%] men; median [interquartile range] age, 60 [50-69] years), 64 (10.8%) reported favourable neurological outcomes. The C-statistic of the TiPS65 score was 0.729 (95% confidence interval (CI): 0.672-0.786). When the cut-off of TiPS65 score was set to >1, the sensitivity and specificity were 0.906 (95%CI: 0.807-0.965) and 0.430 (95%CI: 0.387-0.473), respectively; conversely, when the cut-off was set to >3, they were 0.172 (95%CI: 0.089-0.287) and 0.971 (95%CI: 0.953-0.984), respectively. CONCLUSIONS: The TiPS65 score shows reasonable discrimination and predictive performances. This score can be supportive in the decision-making process for the selection of eligible patients for ECPR in clinical settings.

How Do Looming and Receding Emotional Faces Modulate Duration Perception?

The direction of visual motion has been shown to affect the perception of interval duration; objects moving towards an observer (i.e., looming) are perceived to last longer than objects moving away (i.e., receding), and this has been explained in terms of arousal- or attention-based modulation. To dissociate the two competing accounts, we investigated how the influence of motion direction on duration perception is modulated by the emotional content of stimuli. Participants were given the temporal bisection task with images of emotional faces (angry, happy, and neutral) presented in a static (Experiment 1) or dynamic (Experiment 2) display. In Experiment 1, we found no influence of facial emotion on perceived duration. In Experiment 2, however, looming (i.e., expanding) stimuli were perceived as lasting longer than receding (contracting) ones. More importantly, we found an interaction between participant-rated arousal to faces and motion direction: The looming/receding asymmetry was pronounced when the stimulus arousal was rated low, but this asymmetry diminished with increasing arousal ratings. Thus, looming/receding temporal asymmetry seems to be reduced when arousing facial expressions enhance attentional engagement.