The efficacy of socially assistive robots in improving children's pain and negative affectivity during needle-based invasive treatment: A systematic review and meta-analysis.

BACKGROUND: The ability of socially assistive robots (SARs) to treat dementia and Alzheimer's disease has been verified. Currently, to increase the range of their application, there is an increasing amount of interest in using SARs to relieve pain and negative emotions among children in routine medical settings. However, there is little consensus regarding the use of these robots. OBJECTIVE: This study aimed to evaluate the effect of SARs on pain and negative affectivity among children undergoing invasive needle-based procedures. DESIGN: This study was a systematic review and meta-analysis of randomized controlled trials that was conducted in accordance with the Cochrane Handbook guidelines. METHODS: The PubMed, CINAHL, Web of Science, Cochrane Library, Embase, CNKI, and WanFang databases were searched from inception to January 2024 to identify relevant randomized controlled trials (RCTs). We used the Cochrane Risk of Bias tool 2.0 (RoB2.0) to assess the risk of bias among the included studies, and we used RevMan 5.4 software to conduct the meta-analysis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to assess the quality of the evidence. RESULTS: Ten RCTs involving 815 pediatric subjects were selected for this review and reported outcomes related to pain and emotions during IV placement, port needle insertion, flu vaccination, blood sampling, and dental treatment. Children undergoing needle-related procedures with SARs reported less anxiety (SMD= -0.36; 95% CI= -0.64, -0.09) and fewer distressed avoidance behaviors (SMD= -0.67; 95% CI= -1.04, -0.30) than did those receiving typical care. There were nonsignificant differences between these groups in terms of in pain (SMD = -0.02; 95% CI = - 0.81, 0.78) and fear (SMD = 0.38; 95% CI= -0.06, 0.82). The results of exploratory subgroup analyses revealed no statistically significant differences based on the intervention type of robots or anesthetic use. CONCLUSIONS: The use of SARs is a promising intervention method for alleviating anxiety and distress among children undergoing needle-related procedures. However, additional high-quality randomized controlled trials are needed to further validate these conclusions. TRIAL REGISTRATION: The protocol of this study has been registered in the database PROSPERO (registration ID: CRD42023413279).

Reconstruction of Allen's type IV fingertip amputation via bilateral unequal-sized hallux osteo-onychocutaneous free flaps: A retrospective study with 5-year follow-up.

PURPOSE: The reconstruction of Allen's type IV fingertip amputation is a clinical challenge. Our team designed bilateral unequal-sized hallux osteo-onychocutaneous free flaps for the long-term reconstruction of Allen's type IV fingertip amputation and conducted a retrospective study with a 5-year follow-up aims to evaluate the effects of this technique. METHODS: A retrospective analysis with a 5-year follow-up including 13 patients with Allen's type IV fingertip amputation who were admitted to our hospital from January 2010 to January 2017 was conducted. The patients were treated with bilateral unequal-sized hallux osteo-onychocutaneous free flaps. The operation time, intraoperative blood loss, and complications were recorded, and the survival rate of the transplanted flaps was calculated. During the 5-year follow-up after operation, the nail growth time was recorded and the finger appearance was observed. At the last follow-up appointment, the length, width, and girth of the reconstructed fingertip and contralateral normal fingertip, range of motion of the reconstructed fingertip and contralateral normal fingertip, Semmes-Weinstein test (for the evaluation of tactile sensation), and two-point discrimination testing results were recorded. SPSS 22.0 software was used for the statistical analysis and the data are presented as mean ± SD. RESULTS: The mean operation time was (5.62 ± 0.51) h, the mean intraoperative blood loss was (34.15 ± 3.13) mL, and the survival rate of the transplanted flaps was 100%. During the 5-year follow-up, the average nail growth time was (10.14 ± 1.98) months and the average bone union time was (3.78 ± 0.91) months. The length, width, and girth of the reconstructed fingertip were (31.52 ± 3.73) mm, (17.82 ± 1.74) mm, and (59.75 ± 3.04) mm, respectively, which did not differ from those of the contralateral normal fingertip. The range of motion of the reconstructed fingertip was (12.15 ± 2.79) degrees which is different from that of the contralateral normal fingertip. The average tactile sensation evaluated via the Semmes-Weinstein test and the average two-point discrimination test of the reconstructed fingertip were (0.39 ± 0.17) g and (7.46 ± 1.14) mm, respectively, which were not different from those of the contralateral normal fingertip. The average Maryland score of feet in the donor area was 87.66 ± 7.39, which was satisfactory. CONCLUSION: Bilateral unequal-sized hallux osteo-onychocutaneous free flaps are an effective method to reconstruct Allen's type IV fingertip amputations with a satisfactory appearance and good sensory function.

Development of a Prediction Score for Evaluation of Extubation Readiness in Neurosurgical Patients with Mechanical Ventilation.

BACKGROUND: There is no widely accepted consensus on the weaning and extubating protocols for neurosurgical patients, leading to heterogeneity in clinical practices and high rates of delayed extubation and extubation failure-related health complications. METHODS: In this single-center prospective observational diagnostic study, mechanically ventilated neurosurgical patients with extubation attempts were consecutively enrolled for 1 yr. Responsive physicians were surveyed for the reasons for delayed extubation and developed the Swallowing, Tongue protrusion, Airway protection reflected by spontaneous and suctioning cough, and Glasgow Coma Scale Evaluation (STAGE) score to predict the extubation success for neurosurgical patients already meeting other general extubation criteria. RESULTS: A total of 3,171 patients were screened consecutively, and 226 patients were enrolled in this study. The rates of delayed extubation and extubation failure were 25% (57 of 226) and 19% (43 of 226), respectively. The most common reasons for the extubation delay were weak airway-protecting function and poor consciousness. The area under the receiver operating characteristics curve of the total STAGE score associated with extubation success was 0.72 (95% CI, 0.64 to 0.79). Guided by the highest Youden index, the cutoff point for the STAGE score was set at 6 with 59% (95% CI, 51 to 66%) sensitivity, 74% (95% CI, 59 to 86%) specificity, 90% (95% CI, 84 to 95%) positive predictive value, and 30% (95% CI, 21 to 39%) negative predictive value. At STAGE scores of 9 or higher, the model exhibited a 100% (95% CI, 90 to 100%) specificity and 100% (95% CI, 72 to 100%) positive predictive value for predicting extubation success. CONCLUSIONS: After a survey of the reasons for delayed extubation, the STAGE scoring system was developed to better predict the extubation success rate. This scoring system has promising potential in predicting extubation readiness and may help clinicians avoid delayed extubation and failed extubation-related health complications in neurosurgical patients.

The combination of arterial lactate level with GCS-pupils score to evaluate short term prognosis in traumatic brain injury: a retrospective study.

BACKGROUND: The aim of the study was to determine whether the combination of Glasgow Coma Scale (GCS) and Pupil responses score (GCSP) with arterial lactate level would be an index to predict the short term prognosis in patients with traumatic brain injury (TBI). METHODS: A retrospective study was performed enrolling all TBI patients admitted to intensive care unit (ICU) from 2019 to 2020. The demographics, clinical characteristics, and arterial lactate concentration were recorded. The GCSP and arterial blood analysis (ABG) with lactate was tested as soon as the patient was admitted to ICU. The Glasgow Outcome Scale (GOS) after discharge was regarded as the clinical outcome. A new index named GCSP-L was the combination of GCSP and lactate concentration. GCSP-L was the GCSP score (range 1-15) plus the lactate score (range 0-2). The lactate score was defined based on different lactate concentrations. If lactate was below 2 mmol/L, lactate score was 0, which above 5 mmol/L was 2 and between 2 and 5 mmol/L, the score was 1. As the range of GCSP was 1-15, the range of the GCSP-L was 1 to 17. The area under receiver operating characteristic curve (AUC) was calculated to evaluate the predictive ability of GCSP, lactate and GCSP-L. Statistical significance was set when p value < 0.05. RESULTS: A total of 192 TBI patients were included in the study. Based on GCSP, mild, moderate, and severe TBI were 13.02, 14.06 and 72.92%, respectively. There were 103 (53.65%) patients with the lactate concentration below 2 mmol/L (1.23 ± 0.37 mmol/l), 63 (32.81%) of the range from 2 to 5 (3.04 ± 2.43 mmol/l) and 26 (13.54%) were above 5 mmol/l (7.70 ± 2.43 mmol/l). The AUC was 0.866 (95% CI 0.827-0.904) for GCSP-L, 0.812 (95% CI 0.765-0.858) for GCSP and 0.629 (95% CI 0.570-0.0.688) for lactate. The AUC of GCSP-L was higher than the other two, GCSP and lactate alone. CONCLUSIONS: The combination of GCSP and lactate concentration can be used to predict the short term prognosis in TBI patients.

Use of Electrical Impedance Tomography (EIT) to Estimate Global and Regional Lung Recruitment Volume (VREC) Induced by Positive End-Expiratory Pressure (PEEP): An Experiment in Pigs with Lung Injury.

BACKGROUND Electrical impedance tomography (EIT) is a real-time tool used to monitor lung volume change at the bedside, which could be used to measure lung recruitment volume (VREC) for setting positive end-expiratory pressure (PEEP). We assessed and compared the agreement in VREC measurement with the EIT method versus the flow-derived method. MATERIAL AND METHODS In 12 Bama pigs, lung injury was induced by tracheal instillation of hydrochloric acid and verified by an arterial partial pressure of oxygen to inspired oxygen fraction ratio below 200 mmHg. During the end-expiratory occlusion, an airway release maneuver was conduct at 5 and 15 cmH2O of PEEP. VREC was measured by flow-integrated PEEP-induced lung volume change (flow-derived method) and end-expiratory lung impedance change (EIT-derived method). Linear regression and Bland-Altman analysis were used to test the correlation and agreement between these 2 measures. RESULTS Lung injury was successfully induced in all the animals. EIT-derived VREC was significantly correlated with flow-derived VREC (R²=0.650, p=0.002). The bias (the lower and upper limits of agreement) was -19 (-182 to 144) ml. The median (interquartile range) of EIT-derived VREC was 322 (218-469) ml, with 110 (59-142) ml and 194 (157-307) ml in dependent and nondependent lung regions, respectively. Global and regional respiratory system compliance increased significantly at high PEEP compared to those at low PEEP. CONCLUSIONS Close correlation and agreement were found between EIT-derived and flow-derived VREC measurements. The advantages of EIT-derived recruitability assessment included the avoidance of ventilation interruption and the ability to provide regional recruitment information.

Incidence and risk factors of postoperative delirium in patients admitted to the ICU after elective intracranial surgery: A prospective cohort study.

BACKGROUND: Postoperative delirium (POD) has been confirmed as an important complication after major surgery. However, neurosurgical patients have usually been excluded in previous studies. To date, data on POD and risk factors in patients after intracranial surgery are scarce. OBJECTIVES: To determine the incidence and risk factors of POD in patients after intracranial surgery. DESIGN: Prospective cohort study. SETTING: A neurosurgical ICU of a university-affiliated hospital, Beijing, China. INTERVENTIONS: Adult patients admitted to the ICU after elective intracranial surgery under general anaesthesia were consecutively enrolled between 1 March 2017 and 2 February 2018. Delirium was assessed using the Confusion Assessment Method for the ICU. POD was diagnosed as Confusion Assessment Method for the ICU positive on either postoperative day 1 or day 3. Patients were classified into groups with or without POD. Data were collected for univariate and multivariate analyses to determine the risk factors for POD. RESULTS: A total of 800 patients were included. POD was diagnosed in 157 patients (19.6%, 95% confidence interval 16.9 to 22.4%). Independent risk factors for POD included age, nature of intracranial lesion, frontal approach craniotomy, duration of surgery, presence of an episode of low pulse oxygenation at ICU admission, presence of inadequate emergence and emergence delirium, postoperative pain and presence of immobilising events. POD was associated with adverse outcomes and high costs. CONCLUSION: POD is prevalent in patients after elective intracranial surgery. The identified risk factors for and the potential association of POD with adverse outcomes suggest that a comprehensive strategy involving screening for predisposing factors and early prevention of modifiable factors should be established in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT03087838.

CRISPR/Cas9-mediated efficient and precise targeted integration of donor DNA harboring double cleavage sites in Xenopus tropicalis.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system has emerged as a powerful tool for knock-in of DNA fragments via donor plasmid and homology-independent DNA repair mechanism; however, conventional integration includes unnecessary plasmid backbone and may result in the unfaithful expression of the modified endogenous genes. Here, we report an efficient and precise CRISPR/Cas9-mediated integration strategy using a donor plasmid that harbors 2 of the same cleavage sites that flank the cassette at both sides. After the delivery of donor plasmid, together with Cas9 mRNA and guide RNA, into cells or fertilized eggs, concurrent cleavages at both sides of the exogenous cassette and the desired chromosomal site result in precise targeted integration without plasmid backbone. We successfully used this approach to precisely integrate the EGFP reporter gene into the myh6 locus or the GAPDH locus in Xenopus tropicalis or human cells, respectively. Furthermore, we demonstrate that replacing conventional terminators with the endogenous 3UTR of target genes in the cassette greatly improves the expression of reporter gene after integration. Our efficient and precise method will be useful for a variety of targeted genome modifications, not only in X. tropicalis, but also in mammalian cells, and can be readily adapted to many other organisms.-Mao, C.-Z., Zheng, L., Zhou, Y.-M., Wu, H.-Y., Xia, J.-B., Liang, C.-Q., Guo, X.-F., Peng, W.-T., Zhao, H., Cai, W.-B., Kim, S.-K., Park, K.-S., Cai, D.-Q., Qi, X.-F. CRISPR/Cas9-mediated efficient and precise targeted integration of donor DNA harboring double cleavage sites in Xenopus tropicalis.

Use of the Bispectral Index to Predict Recovery of Consciousness in Patients with Spontaneous Intracerebral Hemorrhage After Surgical Hematoma Evacuation: A Prospective Cohort Study.

BACKGROUND Our study aimed to test the predictive value of the bispectral index (BIS) for the post-operational consciousness recovery in patients undergone hematoma evacuation due to spontaneous intracerebral hemorrhage (ICH). MATERIAL AND METHODS In this prospective cohort study, we enrolled adult spontaneous ICH patients after surgical hematoma evacuation who did not recover consciousness on the first postoperative day. After patient enrollment, the BIS was continuously monitored for 12 hours, and the motor response on the Glasgow Coma Scale (GCS-M) was evaluated. The patients were followed up for 30 days and divided into a consciousness recovery group and a nonrecovery group. Receiver operating characteristic curve analysis was performed to investigate the predictive values of the BIS, GCS-M and ICH score on the consciousness recovery. The area under the curve (AUC) and 95% confidence interval (95%CI) were calculated. During the 12-hour monitoring period, the peak BIS value after GCS-M stimulation was used for ROC analysis. RESULTS Of the 55 enrolled patients, 19 patients recovered consciousness, and 36 patients did not. The BIS value of the consciousness recovery group was significantly higher than that of the nonrecovery group (P<0.001). For consciousness recovery prediction, the AUC (95%CI) of the BIS values after external stimulation was 0.97 (0.91-1.00), which was superior to the GCS-M (0.75 [0.59-0.91]) and ICH score (0.57 [0.41-0.73]). CONCLUSIONS Our study demonstrates that BIS might be a potential tool for predicting the consciousness recovery in ICH patients undergone surgical hematoma evacuation.

A bibliometric analysis of respiratory mechanics research related to acute respiratory distress syndrome from 1985 to 2023.

Background: Acute respiratory distress syndrome (ARDS) is a severe condition characterized by lung stiffness and compromised gas exchange, often requiring mechanical ventilation for treatment. In addition to its clinical significance, understanding the publication trends and research patterns in respiratory mechanics related to ARDS can provide insights into the evolution of this field from a bibliometric perspective, aiding in strategic planning and resource allocation for future research endeavors. Objective: This study aimed to explore the trends and identify the hotspots in respiratory mechanics research related to ARDS. Methods: All relevant studies on respiratory mechanics of ARDS published between 1985 and 2023 were retrieved from the Web of Science Core Collection (WoSCC), and the retrieval strategy was topic search "TS = respiratory mechanics OR lung mechanics AND TS = ARDS OR acute respiratory distress syndrome." Annual trends, citation patterns, and contributions from countries, institutions, authors, and journals were analyzed using Bibliometrix Biblioshiny. Networks and overlay of authors, institutions, countries, journals, co-citations, and keywords were analyzed and visualized using VOSviewer. Results: Our analysis included 1,248 articles published between 1985 and 2023, revealing fluctuations in publication output over time. The United States emerged as the leading contributor, with Critical Care Medicine being the most prominent journal. Key research themes included mechanical ventilation, acute lung injury, and protective ventilation strategies. International collaboration was evident, facilitating knowledge exchange and interdisciplinary cooperation. Conclusion: Our study sheds light on the evolving landscape of respiratory mechanics research in ARDS. International collaboration is pivotal in advancing the field, while researchers increasingly focus on personalized approaches to address the complexities of ARDS respiratory mechanics.

Use of pressure muscle index to predict the contribution of patient's inspiratory effort during pressure support ventilation: a prospective physiological study.

Background: The successful implementation of assisted ventilation depends on matching the patient's effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient's inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient's effort during ventilator support. Methods: In this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to -1, 0, +1, +2, and + 3 cm H2O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure-time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient's inspiratory effort. Results: A total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H2O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10-12) to 5 (4-6) cm H2O (p < 0.001), which resulted in a significant increase in pressure-time products of respiratory muscle [from 2.9 (2.1-5.0) to 6.8 (5.3-8.1) cm H2O•s] and the fraction of pressure generated by the patient [from 25% (19-31%) to 72% (62-87%)] (p < 0.001). The area under receiver operating characteristic curves for PMI to predict 30 and 70% contribution of patient's effort were 0.93 and 0.95, respectively. High sensitivity (all 1.00), specificity (0.86 and 0.78), and negative predictive value (all 1.00), but low positive predictive value (0.61 and 0.43) were obtained to predict either high or low contribution of patient's effort. Conclusion: Our results preliminarily suggested the feasibility of pressure support adjustment according to the PMI target from the ventilator screen. PMI could reliably predict the high and low contribution of a patient's effort during assisted ventilation.Clinical trial registration: ClinicalTrials.gov, identifier NCT05970393.

Delta radiomics analysis for prediction of intermediary- and high-risk factors for patients with locally advanced cervical cancer receiving neoadjuvant therapy.

This study aimed to assess the feasibility of using magnetic resonance imaging (MRI)-based Delta radiomics characteristics extrapolated from the Ax LAVA + C series to identify intermediary- and high-risk factors in patients with cervical cancer undergoing surgery following neoadjuvant chemoradiotherapy. A total of 157 patients were divided into two groups: those without any intermediary- or high-risk factors and those with one intermediary-risk factor (negative group; n = 75). Those with any high-risk factor or more than one intermediary-risk factor (positive group; n = 82). Radiomics characteristics were extracted using Ax-LAVA + C MRI sequences. The data was divided into training (n = 126) and test (n = 31) sets in an 8:2 ratio. The training set data features were selected using the Mann-Whitney U test and the Least Absolute Shrinkage and Selection Operator (LASSO) test. The best radiomics features were then analyzed to build a preoperative predictive radiomics model for predicting intermediary- and high-risk factors in cervical cancer. Three models-the clinical model, the radiomics model, and the combined clinic and radiomics model-were developed in this study utilizing the random forest Algorithm. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), accuracy, sensitivity, and specificity were used to assess the predictive efficacy and clinical benefits of each model. Three models were developed in this study to predict intermediary- and high-risk variables associated with postoperative pathology for patients who underwent surgery after receiving neoadjuvant radiation. In the training and test sets, the AUC values assessed using the clinical model, radiomics model, and combined clinical and radiomics models were 0.76 and 0.70, 0.88 and 0.86, and 0.91 and 0.89, respectively. The use of machine learning algorithms to analyze Delta Ax LAVA + C MRI radiomics features can aid in the prediction of intermediary- and high-risk factors in patients with cervical cancer receiving neoadjuvant therapy.

Ineffective Effort in Patients With Acute Brain Injury Undergoing Invasive Mechanical Ventilation.

BACKGROUND: Ineffective effort (IE) is a frequent patient-ventilator asynchrony in invasive mechanical ventilation. This study aimed to investigate the incidence of IE and to explore its relationship with respiratory drive in subjects with acute brain injury undergoing invasive mechanical ventilation. METHODS: We retrospectively analyzed a clinical database that assessed patient-ventilator asynchrony in subjects with acute brain injury. IE was identified based on airway pressure, flow, and esophageal pressure waveforms collected at 15-min intervals 4 times daily. At the end of each data set recording, airway-occlusion pressure (P0.1) was determined by the airway occlusion test. IE index was calculated to indicate the severity of IE. The incidence of IE in different types of brain injuries as well as its relationship with P0.1 was determined. RESULTS: We analyzed 852 data sets of 71 subjects with P0.1 measured and undergoing mechanical ventilation for at least 3 d after enrollment. IE was detected in 688 (80.8%) data sets, with a median index of 2.2% (interquartile range 0.4-13.1). Severe IE (IE index ≥ 10%) was detected in 246 (28.9%) data sets. The post craniotomy for brain tumor and the stroke groups had higher median IE index and lower P0.1 compared with the traumatic brain injury group (2.6% [0.7-9.7] vs 2.7% [0.3-21] vs 1.2% [0.1-8.5], P = .002; 1.4 [1-2] cm H2O vs 1.5 [1-2.2] cm H2O vs 1.8 [1.1-2.8] cm H2O, P = .001). Low respiratory drive (P0.1 < 1.14 cm H2O) was independently associated with severe IE in the expiratory phase (IEE) even after adjusting for confounding factors by logistic regression analysis (odds ratio 5.18 [95% CI 2.69-10], P < .001). CONCLUSIONS: IE was very common in subjects with acute brain injury. Low respiratory drive was independently associated with severe IEE.

Use of airway pressure-based indices to detect high and low inspiratory effort during pressure support ventilation: a diagnostic accuracy study.

BACKGROUND: Assessment of the patient's respiratory effort is essential during assisted ventilation. We aimed to evaluate the accuracy of airway pressure (Paw)-based indices to detect potential injurious inspiratory effort during pressure support (PS) ventilation. METHODS: In this prospective diagnostic accuracy study conducted in four ICUs in two academic hospitals, 28 adult acute respiratory failure patients undergoing PS ventilation were enrolled. A downward PS titration was conducted from 20 cmH2O to 2 cmH2O at a 2 cmH2O interval. By performing an end-expiratory airway occlusion maneuver, the negative Paw generated during the first 100 ms (P0.1) and the maximal negative swing of Paw (∆Pocc) were measured. After an end-inspiratory airway occlusion, Paw reached a plateau, and the magnitude of change in plateau from peak Paw was measured as pressure muscle index (PMI). Esophageal pressure was monitored and inspiratory muscle pressure (Pmus) and Pmus-time product per minute (PTPmus/min) were used as the reference standard for the patient's effort. High and low effort was defined as Pmus > 10 and < 5 cmH2O, or PTPmus/min > 200 and < 50 cmH2O s min-1, respectively. RESULTS: A total of 246 levels of PS were tested. The low inspiratory effort was diagnosed in 145 (59.0%) and 136 (55.3%) PS levels using respective Pmus and PTPmus/min criterion. The receiver operating characteristic area of the three Paw-based indices by the respective two criteria ranged from 0.87 to 0.95, and balanced sensitivity (0.83-0.96), specificity (0.74-0.88), and positive (0.80-0.91) and negative predictive values (0.78-0.94) were obtained. The high effort was diagnosed in 34 (13.8%) and 17 (6.9%) support levels using Pmus and PTPmus/min criterion, respectively. High receiver operating characteristic areas of the three Paw-based indices by the two criteria were found (0.93-0.95). A high sensitivity (0.80-1.00) and negative predictive value (0.97-1.00) were found with a low positive predictive value (0.23-0.64). CONCLUSIONS: By performing simple airway occlusion maneuvers, the Paw-based indices could be reliably used to detect low inspiratory efforts. Non-invasive and easily accessible characteristics support their potential bedside use for avoiding over-assistance. More evaluation of their performance is required in cohorts with high effort.

An Apical Resection Model in the Adult Xenopus tropicalis Heart.

It is known that in adult mammals, the heart has lost its regenerative capacity, making heart failure one of the leading causes of death worldwide. Previous research has demonstrated the regenerative ability of the heart of the adult Xenopus tropicalis, an anuran amphibian with a diploid genome and a close evolutionary relationship with mammals. Additionally, studies have shown that following ventricular apex resection, the heart can regenerate without scarring in X. tropicalis. Consequently, these previous results suggest that X. tropicalis is an appropriate alternative vertebrate model for the study of adult heart regeneration. A surgical model of cardiac regeneration in the adult X. tropicalis is presented herein. Briefly, the frogs were anesthetized and fixed; then, a small incision was made with iridectomy scissors, penetrating the skin and pericardium. Gentle pressure was applied to the ventricle, and the apex of the ventricle was then cut out with scissors. Cardiac injury and regeneration were confirmed by histology at 7-30 days post resection (dpr). This protocol established an apical resection model in adult X. tropicalis, which can be employed to elucidate the mechanisms of adult heart regeneration.

Validation of the flow index to detect low inspiratory effort during pressure support ventilation.

BACKGROUND: Bedside assessment of low levels of inspiratory effort, which are probably insufficient to prevent muscle atrophy, is challenging. The flow index, which is derived from the analysis of the inspiratory portion of the flow-time waveform, has been recently introduced as a non-invasive parameter to evaluate the inspiratory effort. The primary objective of the present study was to provide an external validation of the flow index to detect low inspiratory effort. METHODS: Datasets containing flow, airway pressure, and esophageal pressure (Pes)-time waveforms were obtained from a previously published study in 100 acute brain-injured patients undergoing pressure support ventilation. Waveforms data were analyzed offline. A low inspiratory effort was defined by one of the following criteria, work of breathing (WOB) less than 0.3 J/L, Pes-time product (PTPes) per minute less than 50 cmH2O•s/min, or inspiratory muscle pressure (Pmus) less than 5 cmH2O, adding "or occurrence of ineffective effort more than 10%" for all criteria. The flow index was calculated according to previously reported method. The association of flow index with Pes-derived parameters of effort was investigated. The diagnostic accuracy of the flow index to detect low effort was analyzed. RESULTS: Moderate correlations were found between flow index and WOB, Pmus, and PTPes per breath and per minute (Pearson's correlation coefficients ranged from 0.546 to 0.634, P < 0.001). The incidence of low inspiratory effort was 62%, 51%, and 55% using the definition of WOB, PTPes per minute, and Pmus, respectively. The area under the receiver operating characteristic curve for flow index to diagnose low effort was 0.88, 0.81, and 0.88, for the three respective definition. By using the cutoff value of flow index less than 2.1, the diagnostic performance for the three definitions showed sensitivity of 0.95-0.96, specificity of 0.57-0.71, positive predictive value of 0.70-0.84, and negative predictive value of 0.90-0.93. CONCLUSIONS: The flow index is associated with Pes-based inspiratory effort measurements. Flow index can be used as a valid instrument to screen low inspiratory effort with a high probability to exclude cases without the condition.

A U-shaped association of tracheostomy timing with all-cause mortality in mechanically ventilated patients admitted to the intensive care unit: A retrospective cohort study.

Objectives: To evaluate the association of tracheostomy timing with all-cause mortality in patients with mechanical ventilation (MV). Method: It's a retrospective cohort study. Adult patients undergoing invasive MV who received tracheostomy during the same hospitalization based on the Medical Information Mart for Intensive Care-III (MIMIC-III) database, were selected. The primary outcome was the relationship between tracheostomy timing and 90-day all-cause mortality. A restricted cubic spline was used to analyze the potential non-linear correlation between tracheostomy timing and 90-day all-cause mortality. The secondary outcomes included free days of MV, incidence of ventilator-associated pneumonia (VAP), free days of analgesia/sedation in the intensive care unit (ICU), length of stay (LOS) in the ICU, LOS in hospital, in-ICU mortality, and 30-day all-cause mortality. Results: A total of 1,209 patients were included in this study, of these, 163 (13.5%) patients underwent tracheostomy within 4 days after intubation, while 647 (53.5%) patients underwent tracheostomy more than 11 days after intubation. The tracheotomy timing showed a U-shaped relationship with all-cause mortality, patients who underwent tracheostomy between 5 and 10 days had the lowest 90-day mortality rate compared with patients who underwent tracheostomy within 4 days and after 11 days [84 (21.1%) vs. 40 (24.5%) and 206 (31.8%), P < 0.001]. Conclusion: The tracheotomy timing showed a U-shaped relationship with all-cause mortality, and the risk of mortality was lowest on day 8, but a causal relationship has not been demonstrated.

Mettl3-mediated m6A modification of Fgf16 restricts cardiomyocyte proliferation during heart regeneration.

Cardiovascular disease is the leading cause of death worldwide due to the inability of adult heart to regenerate after injury. N6-methyladenosine (m6A) methylation catalyzed by the enzyme methyltransferase-like 3 (Mettl3) plays an important role in various physiological and pathological bioprocesses. However, the role of m6A in heart regeneration remains largely unclear. To study m6A function in heart regeneration, we modulated Mettl3 expression in vitro and in vivo. Knockdown of Mettl3 significantly increased the proliferation of cardiomyocytes and accelerated heart regeneration following heart injury in neonatal and adult mice. However, Mettl3 overexpression decreased cardiomyocyte proliferation and suppressed heart regeneration in postnatal mice. Conjoint analysis of methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq identified Fgf16 as a downstream target of Mettl3-mediated m6A modification during postnatal heart regeneration. RIP-qPCR and luciferase reporter assays revealed that Mettl3 negatively regulates Fgf16 mRNA expression in an m6A-Ythdf2-dependent manner. The silencing of Fgf16 suppressed the proliferation of cardiomyocytes. However, the overexpression of ΔFgf16, in which the m6A consensus sequence was mutated, significantly increased cardiomyocyte proliferation and accelerated heart regeneration in postnatal mice compared with wild-type Fgf16. Our data demonstrate that Mettl3 post-transcriptionally reduces Fgf16 mRNA levels through an m6A-Ythdf2-dependen pathway, thereby controlling cardiomyocyte proliferation and heart regeneration.

Cardiovascular diseases are one of the world's biggest killers. Even for patients who survive a heart attack, recovery can be difficult. This is because ­ unlike some amphibians and fish ­ humans lack the ability to produce enough new heart muscle cells to replace damaged tissue after a heart injury. In other words, the human heart cannot repair itself. Molecules known as messenger RNA (mRNA) carry the 'instructions' from the DNA inside the cell nucleus to its protein-making machinery in the cytoplasm of the cell. These messenger molecules can also be altered by different enzymes that attach or remove chemical groups. These modifications can change the stability of the mRNA, or even 'silence' it altogether by stopping it from interacting with the protein-making machinery, thus halting production of the protein it encodes. For example, a protein called Mettl3 can attach a methyl group to a specific part of the mRNA, causing a reversible mRNA modification known as m⁶A. This type of alteration has been shown to play a role in many conditions, including heart disease, but it has been unclear whether m⁶A could also be important for the regeneration of heart tissue. To find out more, Jiang, Liu, Chen et al. studied heart injury in mice of various ages. Newborn mice can regenerate their heart muscle for a short time, but adult mice lack this ability, which makes them a useful model to study heart disease. Analyses of the proteins and mRNAs in mouse heart cells confirmed that both Mettl3 and m⁶A-modified mRNAs were present. The amount of each also increased with age. Next, experiments in genetically manipulated mice revealed that removing Mettl3 greatly improved tissue repair after heart injury in both newborn and adult mice. In contrast, mouse hearts that produced abnormally high quantities of Mettl3 were unable to regenerate ­ even if the mice were young. Moreover, a detailed analysis of gene activity revealed that Mettl3 was suppressing heart regeneration by decreasing the production of a growth-promoting protein called FGF16. These results reveal a key biological mechanism controlling the heart's ability to repair itself after injury. In the future, Jiang et al. hope that Mettl3 can be harnessed for new, effective therapies to promote heart regeneration in patients suffering from heart disease.

FoxO3 restricts liver regeneration by suppressing the proliferation of hepatocytes.

Upon injury, the liver is capable of substantial regeneration from the original tissue until an appropriate functional size. The underlying mechanisms controlling the liver regeneration processes are not well elucidated. Previous studies have proposed that the transcription factor FoxO3 is involved in various liver diseases, but its exact role in the regulation of liver regeneration remains largely unclear. To directly test the detailed role of FoxO3 in liver regeneration, both a constitutive Albumin-Cre driver line and adeno-associated virus serotype 8 (AAV8)-Tbg-Cre (AAV-Cre)-injected adult FoxO3fl/fl mice were subjected to 70% partial hepatectomy (PH). Our data demonstrate that FoxO3 deletion accelerates liver regeneration primarily by limiting polyploidization and promoting the proliferation of hepatocytes during liver regeneration. RNA-seq analysis indicates that FoxO3 deficiency greatly alters the expression of gene sets associated with cell proliferation and apoptosis during liver regeneration. Chromatin immunoprecipitation-PCR (ChIP-PCR) and luciferase reporter assays reveal that FoxO3 promotes the expression of Nox4 but suppresses the expression of Nr4a1 in hepatocytes. AAV8 virus-mediated overexpression of Nox4 and knockdown of Nr4a1 significantly suppressed hepatocyte proliferation and liver regeneration in FoxO3-deficient mice. We demonstrate that FoxO3 negatively controls hepatocyte proliferation through Nox4 upregulation and Nr4a1 downregulation, thereby ensuring appropriate functional regeneration of the liver. Our findings provide novel mechanistic insight into the therapeutic mechanisms of FoxO3 in liver damage and repair.

[Effect and Mechanism of Foliar Application Nano-MnO2 on Cadmium Enrichment of Rice].

Cadmium (Cd) is easily enriched in rice, resulting in an excessive Cd content in the grain, which seriously threatens human health. Manganese (Mn) is an essential element of plants. In a field experiment on Cd-contaminated acid soils, we investigated the effectiveness and mechanism of Mn in minimizing Cd accumulation in rice via foliar spraying using 0.1%, 0.3%, and 0.5% nano-MnO2 solutions at an early stage of heading. Compared with a control treatment, foliar spraying effectively reduced the Cd content of rice leaves, husks, and brown rice; increased the Mn content of all rice organs; but had no effect on rice yield. Foliar application of nano-MnO2 alleviated the plant stress induced by Cd by improving leaf photosynthesis, inhibiting lipid peroxidation, and increasing the content of the oxidative stress protein kinase. In addition, foliar application of nano-MnO2 limited the absorption of Cd by roots by increasing the content of iron-manganese plaque on the surfaces of rice roots and strengthening its adsorption/co-precipitation of Cd. Therefore, foliar application of nano-MnO2 during the early stages of rice heading is an effective measure to increase the Mn content and reduce the Cd content of brown rice.