HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage.

Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions. The data suggested a role for Env glycoform heterogeneity in the activation of the lineage germline B cell. Finally, we showed that localized diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env evolution pattern described for another donor who developed V2-apex targeting bnAbs. Overall, these findings suggest potential strategies for vaccine approaches based on germline-targeting and serial immunogen design.

A general mechanism for transcription bubble nucleation in bacteria.

Bacterial transcription initiation requires σ factors for nucleation of the transcription bubble. The canonical housekeeping σ factor, σ70, nucleates DNA melting via recognition of conserved bases of the promoter -10 motif, which are unstacked and captured in pockets of σ70. By contrast, the mechanism of transcription bubble nucleation and formation during the unrelated σN-mediated transcription initiation is poorly understood. Herein, we combine structural and biochemical approaches to establish that σN, like σ70, captures a flipped, unstacked base in a pocket formed between its N-terminal region I (RI) and extra-long helix features. Strikingly, RI inserts into the nascent bubble to stabilize the nucleated bubble prior to engagement of the obligate ATPase activator. Our data suggest a general paradigm of transcription initiation that requires σ factors to nucleate an early melted intermediate prior to productive RNA synthesis.

Improving the secretion of designed protein assemblies through negative design of cryptic transmembrane domains.

Computationally designed protein nanoparticles have recently emerged as a promising platform for the development of new vaccines and biologics. For many applications, secretion of designed nanoparticles from eukaryotic cells would be advantageous, but in practice, they often secrete poorly. Here we show that designed hydrophobic interfaces that drive nanoparticle assembly are often predicted to form cryptic transmembrane domains, suggesting that interaction with the membrane insertion machinery could limit efficient secretion. We develop a general computational protocol, the Degreaser, to design away cryptic transmembrane domains without sacrificing protein stability. The retroactive application of the Degreaser to previously designed nanoparticle components and nanoparticles considerably improves secretion, and modular integration of the Degreaser into design pipelines results in new nanoparticles that secrete as robustly as naturally occurring protein assemblies. Both the Degreaser protocol and the nanoparticles we describe may be broadly useful in biotechnological applications.

High-resolution single-particle imaging at 100-200 keV with the Gatan Alpine direct electron detector.

Developments in direct electron detector technology have played a pivotal role in enabling high-resolution structural studies by cryo-EM at 200 and 300 keV. Yet, theory and recent experiments indicate advantages to imaging at 100 keV, energies for which the current detectors have not been optimized. In this study, we evaluated the Gatan Alpine detector, designed for operation at 100 and 200 keV. Compared to the Gatan K3, Alpine demonstrated a significant DQE improvement at these energies, specifically a âˆ¼ 4-fold improvement at Nyquist at 100 keV. In single-particle cryo-EM experiments, Alpine datasets yielded better than 2 Å resolution reconstructions of apoferritin at 120 and 200 keV on a ThermoFisher Scientific (TFS) Glacios microscope fitted with a non-standard SP-Twin lens. We also achieved a âˆ¼ 3.2 Å resolution reconstruction of a 115 kDa asymmetric protein complex, proving Alpine's effectiveness with complex biological samples. In-depth analysis revealed that Alpine reconstructions are comparable to K3 reconstructions at 200 keV, and remarkably, reconstruction from Alpine at 120 keV on a TFS Glacios surpassed all but the 300 keV data from a TFS Titan Krios with GIF/K3. Additionally, we show Alpine's capability for high-resolution data acquisition and screening on lower-end systems by obtaining âˆ¼ 3 Å resolution reconstructions of apoferritin and aldolase at 100 keV and detailed 2D averages of a 55 kDa sample using a side-entry cryo holder. Overall, we show that Gatan Alpine performs well with the standard 200 keV imaging systems and may potentially capture the benefits of lower accelerating voltages, bringing smaller sized particles within the scope of cryo-EM.

Prehospital Shock Index Multiplied by the Alert/Verbal/Painful/Unresponsive Score as a Predictor of Clinical Outcomes in Traumatic Injury.

OBJECTIVE: Various prediction scores have been developed to predict mortality in trauma patients, such as the shock index (SI), modified SI (mSI), age-adjusted SI (aSI), and the shock index (SI) multiplied by the alert/verbal/painful/unresponsive (AVPU) score (SIAVPU). The SIAVPU is a novel scoring system but its prediction accuracy for trauma outcomes remains in need of further validation. Therefore, we investigated the accuracy of four scoring systems, including SI, mSI, aSI, and SIAVPU, in predicting mortality, admission to the intensive care unit (ICU), and prolonged hospital length of stay ≥ 30 days (LOS). METHODS: This retrospective multicenter study used data from the Tzu Chi Hospital trauma database. The area under the receiver operating characteristic curve (AUROC) was determined for each outcome to assess their discrimination capabilities and comparing by Delong's test. Subgroup analyses were conducted to investigate the prediction accuracy of the SIAVPU in different patient populations. RESULTS: In total, 5355 patients were included in the analysis. The median of SIAVPU were significantly higher among patients at those with major injury (1.47 vs 0.63), those admitted to the ICU (0.73 vs 0.62), those with prolonged hospital LOS≥ 30 days (0.83 vs 0.64), and those with mortality (1.08 vs 0.64). The AUROC of the SIAVPU was significantly higher than that of the SI, mSI, and aSI for 24-h mortality (AUROC: 0.845 vs 0.533, 0.540, and 0.678), 3-day mortality (AUROC: 0.803 vs 0.513, 0.524, and 0.688), 7-day mortality (AUROC: 0.755 vs 0.494, 0.505, and 0.648), in-hospital mortality (AUROC: 0.722 vs 0.510, 0.524, and 0.667), ICU admission (AUROC: 0.635 vs 0.547, 0.551, and 0.563). At the optimal cutoff value of 0.9, the SIAVPU had an accuracy of 82.2% for predicting 24-h mortality, 82.8% for predicting 3-day mortality, of 82.8% for predicting 7-day mortality, of 82.5% for predicting in-hospital mortality, of 73.9% for predicting Intensive Care Unit (ICU) admission, and of 81.7% for predicting prolonged hospital LOS ≥30 days. CONCLUSIONS: Our results reveal that SIAVPU has better accuracy than the SI, mSI, and aSI for predicting 24-h, 3-day, 7-day, and in-hospital mortality; ICU admission; and prolonged hospital LOS ≥30 days among patients with traumatic injury.

Reverse shock index multiplied by simplified motor score as a predictor of clinical outcomes for patients with COVID-19.

BACKGROUND: The reverse shock index (rSI) combined with the Simplified Motor Score (sMS), that is, the rSI-sMS, is a novel and efficient prehospital triage scoring system for patients with COVID-19. In this study, we evaluated the predictive accuracy of the rSI-sMS for general ward and intensive care unit (ICU) admission among patients with COVID-19 and compared it with that of other measures, including the shock index (SI), modified SI (mSI), rSI combined with the Glasgow Coma Scale (rSI-GCS), and rSI combined with the GCS motor subscale (rSI-GCSM). METHODS: All patients who visited the emergency department of Taipei Tzu Chi Hospital between January 2021 and June 2022 were included in this retrospective cohort. A diagnosis of COVID-19 was confirmed through a SARS-CoV-2 reverse-transcription polymerase chain reaction test or SARS-CoV-2 rapid test with oropharyngeal or nasopharyngeal swabs and was double confirmed by checking International Classification of Diseases, Tenth Revision, Clinical Modification codes in electronic medical records. In-hospital mortality was regarded as the primary outcome, and sepsis, general ward or ICU admission, endotracheal intubation, and total hospital length of stay (LOS) were regarded as secondary outcomes. Multivariate logistic regression was used to determine the relationship between the scoring systems and the three major outcomes of patients with COVID-19, including. The discriminant ability of the predictive scoring systems was investigated using the area under the receiver operating characteristic curve, and the most favorable cutoff value of the rSI-sMS for each major outcome was determined using Youden's index. RESULTS: After 74,183 patients younger than 20 years (n = 11,572) and without COVID-19 (n = 62,611) were excluded, 9,282 patients with COVID-19 (median age: 45 years, interquartile range: 33-60 years, 46.1% men) were identified as eligible for inclusion in the study. The rate of in-hospital mortality was determined to be 0.75%. The rSI-sMS scores were significantly lower in the patient groups with sepsis, hyperlactatemia, admission to a general ward, admission to the ICU, total length of stay ≥ 14 days, and mortality. Compared with the SI, mSI, and rSI-GCSM, the rSI-sMS exhibited a significantly higher accuracy for predicting general ward admission, ICU admission, and mortality but a similar accuracy to that of the rSI-GCS. The optimal cutoff values of the rSI-sMS for predicting general ward admission, ICU admission, and mortality were calculated to be 3.17, 3.45, and 3.15, respectively, with a predictive accuracy of 86.83%, 81.94%%, and 90.96%, respectively. CONCLUSIONS: Compared with the SI, mSI, and rSI-GCSM, the rSI-sMS has a higher predictive accuracy for general ward admission, ICU admission, and mortality among patients with COVID-19.

Parenting self-efficacy and parenting stress mediates the effects of the association of perceived social support and readiness for discharge among parents of children with primary nephrotic syndrome.

PURPOSE: To investigate the level of readiness for discharge among parents of children with primary nephrotic syndrome and to explore the mediating role of parenting self-efficacy and parenting stress between perceived social support and readiness for discharge. DESIGN AND METHODS: A cross-sectional study was conducted in five large tertiary general hospitals in Hunan, China. Data related to demographics, perceived social support, parenting self-efficacy, parenting stress, and readiness for discharge were collected from 350 parents of children diagnosed with primary nephrotic syndrome. Path analysis was used to determine the mediating roles of parenting self-efficacy and parenting stress in the relationship between perceived social support and readiness for discharge. RESULTS: Parents of children with nephrotic syndrome in China experienced low perceived social support, low readiness for discharge, and high parenting stress. Factors influencing readiness for discharge include the child's age, duration of illness, first episode or relapse, parental literacy and marital status. Parenting self-efficacy and parenting stress mediated the effects of the association of perceived social support and readiness for discharge. CONCLUSION: Perceived social support influences the readiness of parents of children with nephrotic syndrome. Parenting self-efficacy and parenting stress have a chain mediating effect of the association of perceived social support and readiness for discharge. PRACTICE IMPLICATIONS: This study emphasizes the mediating role of the psychological state of the child's parents. Nurses should take steps to increase perceived social support and parenting self-efficacy of the child's parents and to reduce parenting stress in order to improve readiness for discharge.

Assessing the Impact of the COVID-19 Pandemic on Pediatric Emergency Department Visits in Taiwan.

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted healthcare systems worldwide. To assess the effects of the pandemic on pediatric emergency department (ED) visits in Taiwan, we conducted a study to evaluate changes in pediatric ED visits during the COVID-19 pandemic. Materials and Methods: This retrospective study included pediatric patients (age ≤ 18) who visited the ED between 21 January 2019 and 30 April 2019, at three hospitals of the Cathay Health System, and compared them with a corresponding period in 2020. Basic information, including mode of arrival, triage level, disposition, chief complaints, and incidence rates, were analyzed before and during the pandemic. Results: A total of 10,116 patients, with 6009 in the pre-pandemic group and 4107 in the pandemic group, were included in this study. The mean number of daily pediatric ED visits decreased from 60.09 before the pandemic to 40.66 during the pandemic, while ambulance use increased significantly by 2.56%. The percentage of patients with high acuity triage levels (levels 1 and 2) was significantly lower during the pandemic period (0.63% and 10.18%, respectively) than the pre-pandemic period (0.7% and 10.9%, respectively). Additionally, a significantly higher proportion of patients were discharged during the pandemic period (89.36%) than during the pre-pandemic period (88.33%). The proportion of COVID-19-related complaints, such as fever and respiratory tract infections, as well as other complaints including gastrointestinal issues, trauma, and psychological problems, significantly increased during the pandemic. Conclusions: In preparation for future pandemics, we recommend increasing emergency medical service capacity, establishing a non-contagious route for obtaining chronic medication prescriptions, optimizing staff allocation in pediatric emergency departments, and increasing the number of hospital social workers for enhanced support.

Association between Time to Emergent Surgery and Outcomes in Trauma Patients: A 10-Year Multicenter Study.

Background: Research on the impact of reduced time to emergent surgery in trauma patients has yielded inconsistent results. Therefore, this study investigated the relationship between waiting emergent surgery time (WEST) and outcomes in trauma patients. Methods: This retrospective, multicenter study used data from the Tzu Chi Hospital trauma database. The primary clinical outcomes were in-hospital mortality, intensive care unit (ICU) admission, and prolonged hospital length of stay (LOS) of ≥30 days. Results: A total of 15,164 patients were analyzed. The median WEST was 444 min, with an interquartile range (IQR) of 248-848 min for all patients. Patients who died in the hospital had a shorter median WEST than did those who survived (240 vs. 446 min, p < 0.001). Among the trauma patients with a WEST of <2 h, the median time was 79 min (IQR = 50-100 min). No significant difference in WEST was observed between the survival and mortality groups for patients with a WEST of <120 min (median WEST: 85 vs. 78 min, p < 0.001). Multivariable logistic regression analysis revealed that WEST was not associated with an increased risk of in-hospital mortality (adjusted odds ratio [aOR] = 1.05, 95% confidence interval [CI] = 0.17-6.35 for 30 min ≤ WEST < 60 min; aOR = 1.12, 95% CI = 0.22-5.70 for 60 min ≤ WEST < 90 min; and aOR = 0.60, 95% CI = 0.13-2.74 for WEST ≥ 90 min). Conclusions: Our findings do not support the "golden hour" concept because no association was identified between the time to definitive care and in-hospital mortality, ICU admission, and prolonged hospital stay of ≥30 days.

Use of Reverse Shock Index Multiplied by Simplified Motor Score in a Five-Level Triage System: Identifying Trauma in Adult Patients at a High Risk of Mortality.

Background and Objectives: The Taiwan Triage and Acuity Scale (TTAS) is reliable for triaging patients in emergency departments in Taiwan; however, most triage decisions are still based on chief complaints. The reverse-shock index (SI) multiplied by the simplified motor score (rSI-sMS) is a more comprehensive approach to triage that combines the SI and a modified consciousness assessment. We investigated the combination of the TTAS and rSI-sMS for triage compared with either parameter alone as well as the SI and modified SI. Materials and Methods: We analyzed 13,144 patients with trauma from the Taipei Tzu Chi Trauma Database. We investigated the prioritization performance of the TTAS, rSI-sMS, and their combination. A subgroup analysis was performed to evaluate the trends in all clinical outcomes for different rSI-sMS values. The sensitivity and specificity of rSI-sMS were investigated at a cutoff value of 4 (based on previous study and the highest score of the Youden Index) in predicting injury severity clinical outcomes under the TTAS system were also investigated. Results: Compared with patients in triage level III, those in triage levels I and II had higher odds ratios for major injury (as indicated by revised trauma score < 7 and injury severity score [ISS] ≥ 16), intensive care unit (ICU) admission, prolonged ICU stay (≥14 days), prolonged hospital stay (≥30 days), and mortality. In all three triage levels, the rSI-sMS < 4 group had severe injury and worse outcomes than the rSI-sMS ≥ 4 group. The TTAS and rSI-sMS had higher area under the receiver operating characteristic curves (AUROCs) for mortality, ICU admission, prolonged ICU stay, and prolonged hospital stay than the SI and modified SI. The combination of the TTAS and rSI-sMS had the highest AUROC for all clinical outcomes. The prediction performance of rSI-sMS < 4 for major injury (ISS ≥ 16) exhibited 81.49% specificity in triage levels I and II and 87.6% specificity in triage level III. The specificity for mortality was 79.2% in triage levels I and II and 87.4% in triage level III. Conclusions: The combination of rSI-sMS and the TTAS yielded superior prioritization performance to TTAS alone. The integration of rSI-sMS and TTAS effectively enhances the efficiency and accuracy of identifying trauma patients at a high risk of mortality.

Hsa-miR-379 down-regulates Rac1/MLK3/JNK/AP-1/Collagen I cascade reaction by targeting connective tissue growth factor in human alveolar basal epithelial A549 cells.

OBJECTIVE: This study was aimed to screen and identify miRNAs that could regulate human CTGF gene and downstream cascade reaction Rac1/MLK3/JNK/AP-1/Collagen I by bioinformatics and experimental means. METHODS: TargetScan and Tarbase were used to predict miRNAs that may have regulatory effects on human CTGF gene. The dual-luciferase reporter gene assay was employed to verify the results obtained in bioinformatics. Human alveolar basal epithelial A549 cells were exposed to silica (SiO2) culture medium for 24 h to establish an in vitro model of pulmonary fibrosis, and bleomycin (BLM) of 100 ng/mL was used as a positive control. The miRNA and mRNA expression levels were determined by RT-qPCR, and the protein levels were measured by western blot in hsa-miR-379-3p overexpression group or not. RESULTS: A total of 9 differentially expressed miRNAs that might regulate the human CTGF gene were predicted. Hsa-miR-379-3p and hsa-miR-411-3p were selected for the subsequent experiments. The results of the dual-luciferase reporter assay showed that hsa-miR-379-3p could bind to CTGF, but hsa-miR-411-3p could not. Compared with the control group, SiO2 exposure (25 and 50 µg/mL) could significantly reduce the expression level of hsa-miR-379-3p in A549 cells. SiO2 exposure (50 µg/mL) could significantly increase the mRNA expression levels of CTGF, Collagen I, Rac1, MLK3, JNK, AP1, and VIM in A549 cells, while CDH1 level was significantly decreased. Compared with SiO2 + NC group, the mRNA expression levels of CTGF, Collagen I, Rac1, MLK3, JNK, AP1, and VIM were significantly decreased, and CDH1 level was significantly higher when hsa-miR-379-3p was overexpressed. At the same time, overexpression of hsa-miR-379-3p improved the protein levels of CTGF, Collagen I, c-Jun and phospho-c-Jun, JNK1 and phospho-JNK1 significantly compared with SiO2 + NC group. CONCLUSION: Hsa-miR-379-3p was demonstrated for the first time that could directly target and down-regulate human CTGF gene, and further affect the expression levels of key genes and proteins in Rac1/MLK3/JNK/AP-1/Collagen I cascade reaction.

Tributyrin Intake Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm in LDLR-/- Mice.

Abdominal aortic aneurysm (AAA) is a multifactorial cardiovascular disease with a high risk of death, and it occurs in the infrarenal aorta with vascular dilatation. High blood pressure acts on the aortic wall, resulting in rupture and causing life-threatening intra-abdominal hemorrhage. Vascular smooth muscle cell (VSMC) dysregulation and extracellular matrix (ECM) degradation, especially elastin breaks, contribute to structural changes in the aortic wall. The pathogenesis of AAA includes the occurrence of oxidative stress, inflammatory cell infiltration, elastic fiber fragmentation, VSMC apoptosis, and phenotypic transformation. Tributyrin (TB) is decomposed by intestinal lipase and has a function similar to that of butyrate. Whether TB has a protective effect against AAA remains uncertain. In the present study, we established an AAA murine model by angiotensin II (AngII) induction in low-density lipoprotein receptor knockout (LDLR-/-) mice and investigated the effects of orally administered TB on the AAA size, ratio of macrophage infiltration, levels of matrix metalloproteinase (MMP) expression, and epigenetic regulation. TB attenuates AngII-induced AAA size and decreases elastin fragmentation, macrophage infiltration, and MMP expression in the medial layer of the aorta and reduces the levels of SBP (systolic blood pressure, p < 0.001) and MMP-2 (p < 0.02) in the serum. TB reduces the AngII-stimulated expression levels of MMP2 (p < 0.05), MMP9 (p < 0.05), MMP12, and MMP14 in human aortic smooth muscle cells (HASMCs). Moreover, TB and valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, suppress AngII receptor type 1 (AT1R, p < 0.05) activation and increase the expression of acetyl histone H3 by HDAC activity inhibition (p < 0.05). Our findings suggest that TB exerts its protective effect by suppressing the activation of HDAC to attenuate the AngII-induced AT1R signaling cascade.

Feasibility and effect of emotional freedom therapy on sleep quality in patients with end-stage renal disease receiving maintenance hemodialysis: A pilot study.

OBJECTIVE: To explore the feasibility and efficacy of emotional freedom therapy (EFT) in improving sleep quality and managing negative emotions in end-stage renal disease patients on maintenance hemodialysis. METHODS: Between May 2021 and February 2022, 66 maintenance hemodialysis patients with sleep problems were recruited and randomized into an intervention and control group. The intervention group underwent a 12-week intervention of EFT. Two groups' hospital anxiety depression scale (HADS) scores, Pittsburgh sleep quality index (PSQI), and interdialysis weight gain (IDWG) before and one week after the formal intervention were collected and compared. Feasibility analysis was performed using a feasibility questionnaire and in-depth interviews with patients. RESULTS: Before the intervention, there was no statistical difference in the anxiety, depression, PSQI scores and IDWG between the two groups. After balancing the effects of gender and pre-intervention scores, two-way ANCOVA results showed that there were statistically significant differences between the two groups after the intervention in terms of anxiety, depression, sleep quality, sleep duration, daytime dysfunction and PSQI total score. However, interactions effect for IDWG was statistically significant. Simple effects analysis revealed a difference in post-intervention IDWG between the intervention and control groups for patients over 65 (p < 0.05). Most patients agreed or strongly agreed that the EFT was easy to schedule and they did not experience difficulties during learning the EFT process (respectively 75% and 71.88%). And 75% of the participants were willing to continue practicing EFT. Qualitative content analysis identified five prominent categories related to feasibility and acceptability: affirmation, benefits, communication, support and trust. CONCLUSION: EFT can relieve anxiety and depression, enhance sleep quality, and improve the physical condition of patients with end-stage renal disease receiving maintenance hemodialysis. As well, the EFT intervention is practicable, acceptable, and perceived as being beneficial to the patient.

Point-of-Care Ultrasonography Helped to Rapidly Detect Pneumomediastinum in a Vomiting Female.

Vomiting-induced pneumomediastinum is a rare presentation and can be a result of alveolar rupture (Mackler effect) or Boerhaave syndrome. Patients diagnosed with Boerhaave syndrome may present with the classic Mackler triad of vomiting, chest pain, and subcutaneous emphysema. However, there exists a large overlap of symptoms accompanying Boerhaave syndrome and the Macklin effect, including retrosternal chest pain, neck discomfort, cough, sore throat, dysphagia, dysphonia, and dyspnea. Boerhaave syndrome is a dangerous condition. Delayed diagnosis of Boerhaave syndrome may worsen sepsis and cause mortality. Therefore, early diagnosis and timely management are important to prevent further complications. Here, we present a case of vomiting-induced pneumomediastinum, which supports the use of bedside ultrasonography to aid in the diagnosis and rapid differentiation of etiology of pneumomediastinum.

A Ten-Year Retrospective Cohort Study on Neck Collar Immobilization in Trauma Patients with Head and Neck Injuries.

Background and Objectives: In the context of prehospital care, spinal immobilization is commonly employed to maintain cervical stability in head and neck injury patients. However, its use in cases of unclear consciousness or major trauma patients is often precautionary, pending the exclusion of unstable spinal injuries through appropriate diagnostic imaging. The impact of prehospital C-spinal immobilization in these specific patient populations remains uncertain. Materials and Methods: We conducted a retrospective cohort study at Taipei Tzu Chi Hospital from January 2009 to May 2019, focusing on trauma patients suspected of head and neck injuries. The primary outcome assessed was in-hospital mortality. We employed multivariable logistic regression to investigate the relationship between prehospital C-spine immobilization and outcomes, while adjusting for various factors such as age, gender, type of traumatic brain injury, Injury Severity Score (ISS), Revised Trauma Score (RTS), and activation of trauma team. Results: Our analysis encompassed 2733 patients. Among these, patients in the unclear consciousness group (GCS ≤ 8) who underwent C-spine immobilization exhibited a higher mortality rate than those without immobilization. However, there was no statistically significant difference in mortality among patients with alert consciousness (GCS > 8). Multivariable logistic regression analysis revealed that advanced age (age ≥ 65), unclear consciousness (GCS ≤ 8), major traumatic injuries (ISS ≥ 16 and RTS ≤ 7), and the use of neck collars for immobilization (adjusted OR: 1.850, 95% CI: 1.240-2.760, p = 0.003) were significantly associated with an increased risk of mortality. Subgroup analysis indicated that C-spine immobilization was significantly linked to an elevated risk of mortality in older adults (age ≥ 65), patients with unclear consciousness (GCS ≤ 8), those with major traumatic injuries (ISS ≥ 16 and RTS ≤ 7), and individuals in shock (shock index > 1). Conclusions: While our findings do not advocate for the complete abandonment of neck collars in all suspected head and neck injury patients, our study suggests that prehospital cervical and spinal immobilization should be applied more selectively in certain head and neck injury populations. This approach is particularly relevant for older individuals (age ≥ 65), those with unclear consciousness (GCS ≤ 8), individuals experiencing major traumatic injuries (ISS ≥ 16 or RTS ≤ 7), and patients in a state of shock (shock index ≥ 1). Our study employs a retrospective cohort design, which may introduce selection bias. Therefore, in the future, there is a need for confirmation of our results through a two-arm randomized controlled trial (RCT) arises, as this design is considered ideal for addressing this issue.

Non-coding RNAs in lung cancer: emerging regulators of angiogenesis.

Lung cancer is the second cancer and the leading cause of tumor-related mortality worldwide. Angiogenesis is a crucial hallmark of cancer development and a promising target in lung cancer. However, the anti-angiogenic drugs currently used in the clinic do not achieve long-term efficacy and are accompanied by severe adverse reactions. Therefore, the development of novel anti-angiogenic therapeutic approaches for lung cancer is urgently needed. Non-coding RNAs (ncRNAs) participate in multiple biological processes in cancers, including tumor angiogenesis. Many studies have demonstrated that ncRNAs play crucial roles in tumor angiogenesis. This review discusses the regulatory functions of different ncRNAs in lung cancer angiogenesis, focusing on the downstream targets and signaling pathways regulated by these ncRNAs. Additionally, given the recent trend towards utilizing ncRNAs as cancer therapeutics, we also discuss the tremendous potential applications of ncRNAs as biomarkers or novel anti-angiogenic tools in lung cancer.

Postoperative Stroke After Type A Aortic Dissection Repair: Hemorrhage Versus Ischemia.

BACKGROUND: Postoperative stroke is a severe and potentially disabling complication following surgical intervention for acute type A aortic dissection (ATAAD). This retrospective study aims to compare the early and late outcomes between patients who had hemorrhagic and ischemic stroke after undergoing ATAAD repair surgery. METHODS: Between January 2007 and June 2020, a total of 685 consecutive patients underwent ATAAD repair at our institution. Patients who had a preoperative stroke or were unconscious at presentation were excluded from this study. Of the 656 included for analysis, 102 (15.5%) patients had a postoperative stroke confirmed by computed tomography angiography. The strokes were classified into the ischemia group (n = 83, 12.7%) and hemorrhage group (n = 19, 2.9%). Clinical features, surgical information, postoperative complications, modified Rankin Scale (mRS) scores after discharge, and 5-year cumulative survival rates were compared. RESULTS: Demographics, comorbidities, and presentations of ATAAD were similar between the two groups, except a higher rate of preoperative antithrombotic medication was found in the hemorrhage group. The hemorrhage group was associated with a higher complexity of aortic arch replacement, longer cardiopulmonary bypass, and aortic clamping times than the ischemia group. A higher in-hospital mortality rate (42.1% versus 20.5%; p = 0.048) and a higher median mRS score at the 3-month follow-up after discharge (6[3-6] versus 4[2-6]; p = 0.027) were found in the hemorrhage group. The hemorrhage group showed a lower 5-year cumulative survival rate (23.4% versus 57.8%; p = 0.003) compared with the ischemia group. CONCLUSIONS: Postoperative hemorrhagic stroke was associated with poorer neurological outcomes and lower survival rates than those with ischemic stroke. Patients who have complex arch replacement, long cardiopulmonary bypass and aortic clamping times are at risk for postoperative hemorrhagic stroke and should have intensive neurological surveillance for early diagnosis and treatment after ATAAD repair surgery.

The association between blood pressure and in-hospital mortality in traumatic brain injury: Evidence from a 10-year analysis in a single-center.

OBJECTIVE: Blood pressure in patients with traumatic brain injury (TBI) is associated with clinical outcome. However, evidence of blood pressure (BP) range is scarce and the association between BP and clinical outcome is mostly controversial. We aimed to investigate the association between blood pressure and clinical outcome in TBI. METHODS: This is a retrospective cohort study using the Taipei Tzu Chi Hospital trauma database from January 2009 to June 2019; totally, 13,114 patients were examined. The primary outcome of this investigation was in-hospital mortality and the secondary outcomes were intensive care unit (ICU) admission rate and prolong ICU stay (defined as stay in ICU ≥ 14 days). Subgroups analysis of Glasgow Coma Scale (GCS) and Triage SBP was also conducted. RESULTS: A total of 1782 traumatic adult patients with TBI (AIS score < 3) were finally included. The cut-off points are 130 mmHg to 149 mmHg in all TBI patients with lower odds ratio of mortality. In different TBI severity, U-shape relationship also presented and we also found that cut-off points of 130 to 149 mmHg in mild TBI and 110 to 129 mmHg in moderate TBI have lower odds ratio of mortality. The mortality is significantly increased in BP below 90 mmHg and above 190 mmHg in TBI patients. CONCLUSIONS: Traumatic brain injury population presented a U-shape relationship between triage SBP and in-hospital mortality. Early resuscitation and correct hypotension/hypertension in TBI population with BP below 90 mmHg and above 190 mmHg may prevent from increased mortality.

The Effect and Safety of Rapid and Gradual Urinary Decompression in Urine Retention: A Systematic Review and Meta-Analysis.

Background and objectives: Trials to evaluate the effect and safety of rapid and gradual urinary decompression have been published for decades. Due to inconclusive results, this study aimed to assess whether rapid bladder decompression increased complications in adults with acute urinary retention. Materials and Methods: We searched the Cochrane Library, EMBASE, Google Scholar, and PubMed databases for articles published from the database inception to 31 August 2021. Studies that compared the effects and complication rates of rapid and gradual urinary decompression in adults with acute urinary retention were included. The primary outcome was post-decompression hematuria, while the secondary outcome was circulatory collapse. Meta-analyses were conducted using random effects models. Sensitivity analyses, tests for publication bias, and trial sequential analyses were conducted. The PROSPERO registration number is CRD42021233457. Results: Overall, four articles were included in the comprehensive analysis, and 435 participants met all the eligibility criteria. In the primary meta-analysis of all four study groups, rapid urinary decompression did not increase the risk of post-decompression hematuria (RR = 0.91; 95% CI: 0.62 to 1.35; p = 0.642). The I2 statistic was 0.0% (p = 0.732), indicating no substantial heterogeneity. In the meta-analysis of randomized controlled studies, the result did not change (RR = 0.89; 95% CI: 0.31 to 2.52; p = 0.824). The Egger's test and Begg test (p = 0.339 and 0.497, respectively) indicated the absence of statistical evidence of publication bias. Leave-one-out sensitivity analysis was conducted and showed the pooled results were robust. In secondary outcome, there were no reported events of circulatory collapse in the current studies. Conclusions: The currently available data suggest that rapid urinary decompression is an effective and safe method with a complication rate similar to that of gradual decompression in an acute urinary retention population. Further large-scale randomized studies are required.

Prediction of Compartment Syndrome after Protobothrops mucrosquamatus Snakebite by Diastolic Retrograde Arterial Flow: A Case Report.

Post-snakebite compartment syndrome (PSCS) is an uncommon but dangerous condition. Compartment syndrome-like symptoms after snakebite by Protobothrops mucrosquamatus (P. mucrosquamatus) are not effective in guiding fasciotomy. Objective evaluation of intracompartmental pressure measurements in patients with suspected PSCS is recommended. However, there is a lack of consensus regarding PSCS and indications for surgical intervention, including the threshold value of chamber pressure. In addition, intracompartmental pressure measurements may not be readily available in all emergency service settings. Measuring intracompartmental pressure in all snakebite patients for early diagnosis of PSCS is impractical. Therefore, identifying risk factors, continuous real-time monitoring tools, and predictive factors for PSCS are important. Sonography has proved useful in identifying the location and extension of edema after a snakebite. In this study, we attempted to use point-of-care ultrasound to manage PSCS in real-time. Here, we describe a rare case of snakebite from P. mucrosquamatus. PSCS was considered as diastolic retrograde arterial flow (DRAF) was noted in the affected limb with a cobblestone-like appearance in the subcutaneous area, indicating that the target artery was compressed. The DRAF sign requires physicians to aggressively administer antivenom to salvage the limb. The patient was administered 31 vials of P. mucrosquamatus antivenom, and fasciotomy was not performed. DRAF is an early sign of the prediction of PSCS.