Dexmedetomidine Inhibits Paraventricular Corticotropin-releasing Hormone Neurons that Attenuate Acute Stress-induced Anxiety-like Behavior in Mice.

BACKGROUND: Dexmedetomidine has repeatedly shown to improve anxiety, but the precise neural mechanisms underlying this effect remain incompletely understood. This study aims to explore the role of corticotropin-releasing hormone-producing hypothalamic paraventricular nucleus (CRHPVN) neurons in mediating the anxiolytic effects of dexmedetomidine. METHODS: A social defeat stress mouse model was used to evaluate the anxiolytic effects induced by dexmedetomidine through the elevated plus maze, open-field test, and measurement of serum stress hormone levels. In vivo Ca2+ signal fiber photometry and ex vivo patch-clamp recordings were used to determine the excitability of CRHPVN neurons and investigate the specific mechanism involved. CRHPVN neuron modulation was achieved through chemogenetic activation or inhibition. RESULTS: Compared with saline, dexmedetomidine (40 µg/kg) alleviated anxiety-like behaviors. Additionally, dexmedetomidine reduced CRHPVN neuronal excitability. Chemogenetic activation of CRHPVN neurons decreased the time spent in the open arms of the elevated plus maze and in the central area of the open-field test. Conversely, chemogenetic inhibition of CRHPVN neurons had the opposite effect. Moreover, the suppressive impact of dexmedetomidine on CRHPVN neurons was attenuated by the α2-receptor antagonist yohimbine. CONCLUSIONS: The results indicate that the anxiety-like effects of dexmedetomidine are mediated via α2-adrenergic receptor-triggered inhibition of CRHPVN neuronal excitability in the hypothalamus.

Distinct circuits in anterior cingulate cortex encode safety assessment and mediate flexibility of fear reactions.

Safety assessment and threat evaluation are crucial for animals to live and survive in the wilderness. However, neural circuits underlying safety assessment and their transformation to mediate flexibility of fear-induced defensive behaviors remain largely unknown. Here, we report that distinct neuronal populations in mouse anterior cingulate cortex (ACC) encode safety status by selectively responding under different contexts of auditory threats, with one preferably activated when an animal staysing in a self-deemed safe zone and another specifically activated in more dangerous environmental settings that led to escape behavior. The safety-responding neurons preferentially target the zona incerta (ZI), which suppresses the superior colliculus (SC) via its GABAergic projection, while the danger-responding neurons preferentially target and excite SC. These distinct corticofugal pathways antagonistically modulate SC responses to threat, resulting in context-dependent expression of fear reactions. Thus, ACC serves as a critical node to encode safety/danger assessment and mediate behavioral flexibility through differential top-down circuits.

Recent Advances in Co3O4-Based Composites: Synthesis and Application in Combustion of Methane.

In recent years, it has been found that adjusting the organizational structure of Co3O4 through solid solution and other methods can effectively improve its catalytic performance for the oxidation of low concentration methane. Its catalytic activity is close to that of metal Pd, which is expected to replace costly noble metal catalysts. Therefore, the in-depth research on the mechanism and methods of Co3O4 microstructure regulation has very important academic value and economic benefits. In this paper, we reviewed the catalytic oxidation mechanism, microstructure regulation mechanism, and methods of nano-Co3O4 on methane gas, which provides reference for the development of high-activity Co3O4-based methane combustion catalysts. Through literature investigation, it is found that the surface energy state of nano-Co3O4 can be adjusted by loading of noble metals, resulting in the reduction of Co-O bond strength, thus accelerating the formation of reactive oxygen species chemical bonds, and improving its catalytic effect. Secondly, the use of metal oxides and non-metallic oxide carriers helps to disperse and stabilize cobalt ions, improve the structural elasticity of Co3O4, and ultimately improve its catalytic performance. In addition, the performance of the catalyst can be improved by adjusting the microstructure of the composite catalyst and optimizing the preparation process. In this review, we summarize the catalytic mechanism and microstructure regulation of nano-Co3O4 and its composite catalysts (embedded with noble metals or combined with metallic and nonmetallic oxides) for methane combustion. Notably, this review delves into the substance of measures that can be used to improve the catalytic performance of Co3O4, highlighting the constructive role of components in composite catalysts that can improve the catalytic capacity of Co3O4. Firstly, the research status of Co3O4 composite catalyst is reviewed in this paper. It is hoped that relevant researchers can get inspiration from this paper and develop high-activity Co3O4-based methane combustion catalyst.

Early coagulopathy after pediatric out-of-hospital cardiac arrest: secondary analysis of a randomized clinical trial.

BACKGROUND: To estimate the incidence, risk factors, and impact on mortality and functional outcomes for early coagulopathy after the return of spontaneous circulation (ROSC) in pediatric out-of-hospital cardiac arrest (OHCA) patients. METHODS: A post hoc analysis of the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial was conducted. Early coagulopathy was defined as presence of at least one of the following coagulation abnormalities upon admission: international standard ratio (INR), platelets, and age-adjusted activated partial thromboplastin time (APTT) within 6 h after OHCA and before therapeutic hypothermia initiation. The outcomes included 28-day mortality and functional prognosis. Multivariable logistic regression models were used to explore risk factors and association between early coagulopathy and outcomes. RESULTS: Of the 227 patients included, 152 (67%) were male and the median age was 2.3 years [interquartile range (IQR), 0.7-8.6 years]. The overall 28-day mortality was 63%. The incidence of early coagulopathy was 46%. Lower age, longer duration of chest compression, lower temperature, and higher white blood cell (WBC) upon admission increased the risk of early coagulopathy. Early coagulopathy [OR, 2.20 (95% CI, 1.12-4.39), P = 0.023] was independently associated with 28-day mortality after adjusting for confounders. CONCLUSIONS: Early coagulopathy occurred in almost half of pediatric patients with OHCA. Lower age, longer duration of chest compression, lower temperature, and higher WBC increased the risk. The development of early coagulopathy was independently associated with increased mortality.

A Review of Cobalt-Containing Nanomaterials, Carbon Nanomaterials and Their Composites in Preparation Methods and Application.

With the increasing demand for sustainable and green energy, electric energy storage technologies have received enough attention and extensive research. Among them, Li-ion batteries (LIBs) are widely used because of their excellent performance, but in practical applications, the electrochemical performance of electrode materials is not satisfactory. Carbon-based materials with high chemical stability, strong conductivity, high specific surface area, and good capacity retention are traditional anode materials in electrochemical energy storage devices, while cobalt-based nano-materials have been widely used in LIBs anodes because of their high theoretical specific capacity. This paper gives a systematic summary of the state of research of cobalt-containing nanomaterials, carbon nanomaterials, and their composites in LIBs anodes. Moreover, the preparation methods of electrode materials and measures to improve electrochemical performance are also summarized. The electrochemical performance of anode materials can be significantly improved by compounding carbon nanomaterials with cobalt nanomaterials. Composite materials have better electrical conductivity, as well as higher cycle ability and reversibility than single materials, and the synergistic effect between them can explain this phenomenon. In addition, the electrochemical performance of materials can be significantly improved by adjusting the microstructure of materials (especially preparing them into porous structures). Among the different microscopic morphologies of materials, porous structure can provide more positions for chimerism of lithium ions, shorten the diffusion distance between electrons and ions, and thus promote the transfer of lithium ions and the diffusion of electrolytes.

Impact of Oxygen Saturation on Mortality in Obese and Non-obese Critically Ill Patients With Mechanical Ventilation: A Retrospective Observational Study.

Background: The main aim of this study was to evaluate the effect of oxygen saturation on mortality in critically ill patients with mechanical ventilation according to obesity status. Methods: We conducted an observational study in mechanically ventilated patients admitted to the ICU retrospectively. Demographic, arterial blood gas, ventilator setting, interventions, and peripheral oxygen saturation (Spo2) during the first 24 h were recorded and analyzed between non-obese and obese patients. The main exposure included Spo2, time-weighted mean Spo2 (TWM-Spo2), and proportion of time spent in different Spo2 (PTS-Spo2) levels. The primary outcome was hospital mortality. We used multivariable logistic regression models to assess the relationship between Spo2 and mortality, as well as the interaction between PTS-Spo2 and obesity status. Results: A total of 25,100 patients were included, of which 10,564 (42%) were obese patients. After adjusting for confounders, compared with TWM-Spo2 of 94-98%, TWM-Spo2 of < =88% (OR 3.572; CI [2.343, 5.455]; p < 0.001) and of 89-93% (OR 1.514; CI [1.343, 1.706]; p < 0.001) were both associated with higher risk of mortality. PTS-Spo2 of 99-100% was associated with increased risk of mortality for obese patients (OR 1.028; 95% CI 1.010-1.046; p = 0.002; Pinteraction = 0.001), while PTS-Spo2 of 89-93% was associated with increased risk of mortality (OR 1.089; 95% CI 1.051-1.128; p < 0.001; Pinteraction = 0.001) for non-obese patients. Conclusions: For obese and non-obese critically ill patients with mechanical ventilation, the impact of oxygen saturation on hospital mortality is different.

Increase in chloride from baseline is independently associated with mortality in intracerebral hemorrhage patients admitted to intensive care unit: A retrospective study.

Background: Hyperchloremia is associated with increased mortality in critically ill patients. The objective of this study was to investigate the association between increased chloride levels and mortality outcomes in intracerebral hemorrhage (ICH) patients admitted to the intensive care unit (ICU). Methods: We performed a retrospective study of all patients diagnosed with ICH and included in the Medical Information Mart for Intensive Care (MIMIC-Ⅲ) from 2001 to 2012. Inclusion criteria were the first diagnosis of ICH, ICU length of stay (LOS) over 72 h, and not receiving hypertonic saline treatment. Serum chloride perturbation within 72 h of admission was evaluated as a predictor of outcomes. The increase in chloride from baseline was dichotomized based on an increase in chloride in 72 h (≤5 mmol/L or >5 mmol/L). The primary outcome was 90-day mortality. Results: A total of 376 patients (54.5% male, median age 70 years, interquartile range:58-79 years) were included. The overall 90-day mortality was 32.2% (n=121), in-hospital mortality was 25.8% (n=97), and Day 2 acute kidney injury (AKI) occurred in 29.0% (n=109) of patients. The prevalence of hyperchloremia on admission, during the first 72 h, and an increase in chloride (>5 mmol/L) were 8.8%, 39.4%, and 42.8%, respectively. After adjusting for confounders, the hazard ratio of increase in chloride (>5 mmol/L) was 1.66 (95% confidence interval:1.05-2.64, P=0.031). An increase in chloride (>5 mmol/L) was associated with a higher odds ratio for 90-day mortality in both the AKI and non-AKI groups. Conclusions: An increase in chloride from baseline is common in adult patients with ICH admitted to ICU. The increase is significantly associated with elevated mortality. These results support the significance of diligently monitoring chloride levels in these patients.

Phasic Off responses of auditory cortex underlie perception of sound duration.

It has been proposed that sound information is separately streamed into onset and offset pathways for parallel processing. However, how offset responses contribute to auditory perception remains unclear. Here, loose-patch and whole-cell recordings in awake mouse primary auditory cortex (A1) reveal that a subset of pyramidal neurons exhibit a transient "Off" response, with its onset tightly time-locked to the sound termination and its frequency tuning similar to that of the transient "On" response. Both responses are characterized by excitation briefly followed by inhibition, with the latter mediated by parvalbumin (PV) inhibitory neurons. Optogenetically manipulating sound-evoked A1 responses at different temporal phases or artificially creating phantom sounds in A1 further reveals that the A1 phasic On and Off responses are critical for perceptual discrimination of sound duration. Our results suggest that perception of sound duration is dependent on precisely encoding its onset and offset timings by phasic On and Off responses.

Selection of homemade mask materials for preventing transmission of COVID-19: A laboratory study.

The Coronavirus Disease 2019 (COVID-19) has swept the whole world with high mortality. Since droplet transmission is the main route of transmission, wearing a mask serves as a crucial preventive measure. However, the virus has spread quite quickly, causing severe mask shortage. Finding alternative materials for homemade masks while ensuring the significant performance indicators will help alleviate the shortage of masks. Referring to the national standard for the "Surgical Mask" of China, 17 materials to be selected for homemade masks were tested in four key indicators: pressure difference, particle filtration efficiency, bacterial filtration efficiency and resistance to surface wetting. Eleven single-layer materials met the standard of pressure difference (≤49 Pa), of which 3 met the standard of resistance to surface wetting (≥3), 1 met the standard of particle filtration efficiency (≥30%), but none met the standard of bacterial filtration efficiency (≥95%). Based on the testing results of single-layer materials, fifteen combinations of paired materials were tested. The results showed that three double-layer materials including double-layer medical non-woven fabric, medical non-woven fabric plus non-woven shopping bag, and medical non-woven fabric plus granular tea towel could meet all the standards of pressure difference, particle filtration efficiency, and resistance to surface wetting, and were close to the standard of the bacterial filtration efficiency. In conclusion, if resources are severely lacking and medical masks cannot be obtained, homemade masks using available materials, based on the results of this study, can minimize the chance of infection to the maximum extent.

Clinicopathological and immunohistochemical features of pulmonary artery sarcoma: A report of three cases and review of the literature.

Pulmonary artery sarcoma (PAS) is an extremely rare and highly malignant tumor that originates in the pulmonary artery. The majority of reported cases of PAS are confirmed by pathological examination subsequent to surgery or by autopsy. The present study reports the clinicopathological characteristics and immunohistochemical phenotypes of three cases of PAS, and aims to facilitate the identification of this lethal disease. In the present study, the data from clinical, histopathological and immunohistochemical examinations of three patients with PAS, whose diagnoses were confirmed by surgical biopsy conducted at the Beijing Anzhen Hospital (Beijing, China) between 2008 and 2012, were retrospectively analyzed. The patients (two women and one man; average age, 41.3 years old) presented with dyspnea on exertion. In addition, two of the patients experienced chest tightness, and one patient experienced intermittent syncope. Computed tomography pulmonary angiography revealed that two of the patients possessed a filling defect in the main, left and right pulmonary arteries, and one patient possessed a filling defect in the right upper pulmonary artery. Macroscopically, the PAS appeared as a mucoid intraluminal or nodular sessile mass spreading along the pulmonary artery. Microscopically, the tumor consisted of spindle cells with fascicular and storiform patterns, and was accompanied by necrosis and stromal myxoid changes. Immunohistochemically, vimentin, desmin and cluster of differentiation 34 were highly expressed in the patient that was diagnosed with intimal sarcoma, while vimentin and α-smooth muscle actin were highly expressed in the other two patients, who were diagnosed with leiomyosarcoma. PAS is often misdiagnosed due to nonspecific clinical manifestations and radiological features. Therefore, the diagnosis of PAS should be based on typical morphological features and immunohistochemical analysis of the tumor tissue.

Efficacy and safety of noninvasive positive pressure ventilation in the treatment of acute respiratory failure after cardiac surgery.

BACKGROUND: Although noninvasive positive pressure ventilation (NPPV) has been successfully used for various kinds of acute respiratory failure, the data are limited regarding its application in postoperative respiratory failure after cardiac surgery. Therefore, we conducted a prospective randomized control study in a university surgical intensive care unit to evaluate the efficacy and safety of NPPV in the treatment of acute respiratory failure after cardiac surgery, and explore the predicting factors of NPPV failure. METHODS: From September 2011 to November 2012 patients with acute respiratory failure after cardiac surgery who had indication for the use of NPPV were randomly divided into a NPPV treatment group (NPPV group) and the conventional treatment group (control group). The between-group differences in the patients' baseline characteristics, re-intubation rate, tracheotomy rate, ventilator associated pneumonia (VAP) incidence, in-hospital mortality, mechanical ventilation time after enrollment (MV time), intensive care unit (ICU) and postoperative hospital stays were compared. The factors that predict NPPV failure were analyzed. RESULTS: During the study period, a total of 139 patients who had acute respiratory failure after cardiac surgery were recorded, and 95 of them met the inclusion criteria, which included 59 males and 36 females with a mean age of (61.5 ± 11.2) years. Forty-three patients underwent coronary artery bypass grafting (CABG), 23 underwent valve surgery, 13 underwent CABG+valve surgery, 13 underwent major vascular surgery, and three underwent other surgeries. The NPPV group had 48 patients and the control group had 47 patients. In the NPPV group, the re-intubation rate was 18.8%, tracheotomy rate was 12.5%, VAP incidence was 0, and the in-hospital mortality was 18.8%, significantly lower than in the control group 80.9%, 29.8%, 17.0% and 38.3% respectively, P < 0.05 or P < 0.01. The MV time and ICU stay (expressed as the median (P25, P75)) were 18.0 (9.2, 35.0) hours and 4.0 (2.0, 5.0) days, which were significantly shorter than in the control group, 96.0 (26.0, 240.0) hours and 6.0 (4.0, 9.0) days respectively, P < 0.05 or P < 0.01. The postoperative hospital stays of the two groups were similar. The univariate analysis showed that the NPPV success subgroup had more patients with acute lung injury (ALI) (17 vs. 0, P = 0.038), fewer patients with pneumonia (2 vs. 7, P < 0.001) and lower acute physiology and chronic health evaluation II (APACHE II) scores (16.1 ± 2.8 vs. 21.8 ± 3.2, P < 0.001). Multivariate analysis showed that pneumonia (P = 0.027) and a high APACHE II score >20 (P = 0.002) were the independent risk factors of NPPV failure. CONCLUSIONS: We conclude that NPPV can be applied in selected patients with acute respiratory failure after cardiac surgery to reduce the need of re-intubation and improve clinical outcome as compared with conventional treatment. Pneumonia and a high APACHE II score >20 might be the independent risk factors of NPPV failure in this group of patients.