-
Cell Death & Disease Jun 2024S100a8/a9, largely released by polymorphonuclear neutrophils (PMNs), belongs to the S100 family of calcium-binding proteins and plays a role in a variety of inflammatory...
S100a8/a9, largely released by polymorphonuclear neutrophils (PMNs), belongs to the S100 family of calcium-binding proteins and plays a role in a variety of inflammatory diseases. Although S100a8/a9 has been reported to trigger endothelial cell apoptosis, the mechanisms of S100a8/a9-induced endothelial dysfunction during sepsis require in-depth research. We demonstrate that high expression levels of S100a8/a9 suppress Ndufa3 expression in mitochondrial complex I via downregulation of Nrf1 expression. Mitochondrial complex I deficiency contributes to NAD-dependent Sirt1 suppression, which induces mitochondrial disorders, including excessive fission and blocked mitophagy, and mtDNA released from damaged mitochondria ultimately activates ZBP1-mediated PANoptosis in endothelial cells. Moreover, based on comprehensive scRNA-seq and bulk RNA-seq analyses, S100A8/A9 neutrophils are closely associated with the circulating endothelial cell count (a useful marker of endothelial damage), and S100A8 is an independent risk factor for poor prognosis in sepsis patients.
Topics: Calgranulin A; Neutrophils; Sepsis; Humans; Calgranulin B; Mitochondria; Electron Transport Complex I; Endothelial Cells; Animals; Mice; Male; Human Umbilical Vein Endothelial Cells; Mitophagy; Mice, Inbred C57BL; Apoptosis
PubMed: 38942784
DOI: 10.1038/s41419-024-06849-6 -
Physiological Reports Jul 2024Supplemental O (hyperoxia) is a critical intervention for premature infants (<34 weeks) but consequently is associated with development of bronchial airway...
Supplemental O (hyperoxia) is a critical intervention for premature infants (<34 weeks) but consequently is associated with development of bronchial airway hyperreactivity (AHR) and asthma. Clinical practice shifted toward the use of moderate hyperoxia (<60% O), but risk for subsequent airway disease remains. In mouse models of moderate hyperoxia, neonatal mice have increased AHR with effects on airway smooth muscle (ASM), a cell type involved in airway tone, bronchodilation, and remodeling. Understanding mechanisms by which moderate O during the perinatal period initiates sustained airway changes is critical to drive therapeutic advancements toward treating airway diseases. We propose that cellular clock factor BMAL1 is functionally important in developing mouse airways. In adult mice, cellular clocks target pathways highly relevant to asthma pathophysiology and Bmal1 deletion increases inflammatory response, worsens lung function, and impacts survival outcomes. Our understanding of BMAL1 in the developing lung is limited, but our previous findings show functional relevance of clocks in human fetal ASM exposed to O. Here, we characterize Bmal1 in our established mouse neonatal hyperoxia model. Our data show that Bmal1 KO deleteriously impacts the developing lung in the context of O and these data highlight the importance of neonatal sex in understanding airway disease.
Topics: Animals; Hyperoxia; ARNTL Transcription Factors; Mice; Female; Animals, Newborn; Male; Lung; Mice, Inbred C57BL; Mice, Knockout; Sex Characteristics
PubMed: 38942729
DOI: 10.14814/phy2.16122 -
Asian Journal of Surgery Jun 2024
PubMed: 38942634
DOI: 10.1016/j.asjsur.2024.06.083 -
Asian Journal of Surgery Jun 2024
PubMed: 38942628
DOI: 10.1016/j.asjsur.2024.06.095 -
Brazilian Journal of Anesthesiology... Jun 2024Preoperative anxiety in children causes negative postoperative outcomes. Parental presence at induction is a non-pharmacological strategy for relieving anxiety;...
BACKGROUND
Preoperative anxiety in children causes negative postoperative outcomes. Parental presence at induction is a non-pharmacological strategy for relieving anxiety; nevertheless, it is not always possible or effective, namely when parents are overly anxious. Parental presence via video has been demonstrated to be useful in other contexts (divorce, criminal court). This study reports the feasibility of a randomized controlled trial to investigate the effect of video parental presence and parental coaching at induction on preoperative anxiety.
METHODS
The study was a randomized, 2 × 2 factorial design trial examining parental presence (virtual vs. physical) and coaching (provided vs. not provided). Feasibility was assessed by enrollment rate, attrition rate, compliance, and staff satisfaction with virtual method with the NASA-Task Load Index (NASA-TLX) and System Usability Scale (SUS). For the children's anxiety and postoperative outcomes, the modified Yale Preoperative Anxiety Scale (mYPAS) and Post-Hospitalization Behavioral Questionnaire (PHBQ) were used. Parental anxiety was evaluated with the State-Trait Anxiety Inventory (STAI) questionnaire.
RESULTS
A total of 41 parent/patient dyads were recruited. The enrollment rate was 32.2%, the attrition rate 25.5%. Compliance was 87.8% for parents and 85% for staff. The SUS was 67.5/100 and 63.5/100 and NASA-TLX was 29.2 (21.5-36.8) and 27.6 (8.2-3.7) for the anesthesiologists and induction nurses, respectively. No statistically significant difference was found in mYPAS, PHBQ and STAI.
CONCLUSION
A randomized controlled trial to explore virtual parental presence effect on preoperative anxiety is feasible. Further studies are needed to investigate its role and the role of parent coaching in reducing preoperative anxiety.
PubMed: 38942079
DOI: 10.1016/j.bjane.2024.844533 -
Biomedicine & Pharmacotherapy =... Jun 2024As a broad-spectrum anticancer drug, cisplatin is widely used in the treatment of tumors in various systems. Unfortunately, several serious side effects of cisplatin...
As a broad-spectrum anticancer drug, cisplatin is widely used in the treatment of tumors in various systems. Unfortunately, several serious side effects of cisplatin limit its clinical application, the most common of which are nephrotoxicity and ototoxicity. Studies have shown that cochlear hair cell degeneration is the main cause of cisplatin-induced hearing loss. However, the mechanism of cisplatin-induced hair cell death remains unclear. The present study aimed to explore the potential role of activating transcription factor 6 (ATF6), an endoplasmic reticulum (ER)-localized protein, on cisplatin-induced ototoxicity in vivo and in vitro. In this study, we observed that cisplatin exposure induced apoptosis of mouse auditory OC-1 cells, accompanied by a significant increase in the expression of ATF6 and C/EBP homologous protein (CHOP). In cell or cochlear culture models, treatment with an ATF6 agonist, an ER homeostasis regulator, significantly ameliorated cisplatin-induced cytotoxicity. Further, our in vivo experiments showed that subcutaneous injection of an ATF6 agonist almost completely prevented outer hair cell loss and significantly alleviated cisplatin-induced auditory brainstem response (ABR) threshold elevation in mice. Collectively, our results revealed the underlying mechanism by which activation of ATF6 significantly improved cisplatin-induced hair cell apoptosis, at least in part by inhibiting apoptosis signal-regulating kinase 1 expression, and demonstrated that pharmacological activation of ATF6-mediated unfolded protein response is a potential treatment for cisplatin-induced ototoxicity.
PubMed: 38941893
DOI: 10.1016/j.biopha.2024.117025 -
Public Health Jun 2024COVID-19 revealed major shortfalls in healthcare workers (HCWs) trained in acute and critical care worldwide, especially in low-resource settings. We aimed to assess...
OBJECTIVES
COVID-19 revealed major shortfalls in healthcare workers (HCWs) trained in acute and critical care worldwide, especially in low-resource settings. We aimed to assess mass online courses' efficacy in preparing HCWs to manage COVID-19 patients and to determine whether rapidly deployed e-learning can enhance their knowledge and confidence during a pandemic.
STUDY DESIGN
Retrospective cohort study.
METHODS
This international retrospective cohort study, led by a large Academic Medical Centre (AMC), was conducted via YouTube and the AMC's online learning platform. From 2020 to 2021, multidisciplinary experts developed and deployed six online training courses based on the latest evidence-based management guidelines. Participants were selected through a voluntary sample following an electronic campaign. Training outcomes were assessed using pre-and post-test questionnaires, evaluation forms, and post-training assessment surveys. Kirkpatrick's Model guided training evaluation to measure self-reported knowledge, clinical skills, and confidence improvement. We also captured the number and type of COVID-19 patients managed by HCWs after the trainings.
RESULTS
Every 22.8 reach/impression and every 1.2 engagements led to a course registration. The 10,425 registrants (56.8% female, 43.1% male) represented 584 medical facilities across 154 cities. The largest segments of participants were students/interns (20.6%) and medical officers (13.4%). Of the 2169 registered participants in courses with tests, 66.9% completed post-tests. Test scores from all courses increased from the initial baseline to subsequent improvement post-course. Participants completing post-training assessment surveys reported that the online courses improved their knowledge and clinical skills (83.5%) and confidence (89.4%). Respondents managed over 19,720 COVID-19 patients after attending the courses, with 47.7% patients being moderately/severely ill.
CONCLUSIONS
Participants' confidence in handling COVID-19 patients is increased by rapidly deploying mass training to a substantial target population through digital tools. The findings present a virtual education and assessment model that can be leveraged for future global public health issues, and estimates for future electronic campaigns to target.
PubMed: 38941682
DOI: 10.1016/j.puhe.2024.05.006 -
Science Advances Jun 2024Bile acids (BAs) metabolism has a significant impact on the pathogenesis of Alzheimer's disease (AD). We found that deoxycholic acid (DCA) increased in brains of AD mice...
Bile acids (BAs) metabolism has a significant impact on the pathogenesis of Alzheimer's disease (AD). We found that deoxycholic acid (DCA) increased in brains of AD mice at an early stage. The enhanced production of DCA induces the up-regulation of the bile acid receptor Takeda G protein-coupled receptor (TGR5), which is also specifically increased in neurons of AD mouse brains at an early stage. The accumulation of exogenous DCA impairs cognitive function in wild-type mice, but not in TGR5 knockout mice. This suggests that TGR5 is the primary receptor mediating these effects of DCA. Furthermore, excitatory neuron-specific knockout of TGR5 ameliorates Aβ pathology and cognition impairments in AD mice. The underlying mechanism linking TGR5 and AD pathology relies on the downstream effectors of TGR5 and the APP production, which is succinctly concluded as a "p-STAT3-APH1-γ-secretase" signaling pathway. Our studies identified the critical role of TGR5 in the pathological development of AD.
Topics: Animals; Humans; Mice; Alzheimer Disease; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Brain; Deoxycholic Acid; Disease Models, Animal; Mice, Knockout; Neurons; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 38941459
DOI: 10.1126/sciadv.ado1855 -
Medicine Jun 2024I-gel has been used in various clinical situations. The study investigated alterations in respiratory parameters following a stepwise lung recruitment maneuver (LRM)... (Observational Study)
Observational Study
I-gel has been used in various clinical situations. The study investigated alterations in respiratory parameters following a stepwise lung recruitment maneuver (LRM) using the i-gel. The research involved 60 patients classified as American Society of Anesthesiologists class I-II, aged 30 to 75 years, undergoing elective urologic surgery. Various respiratory parameters, including lung compliance, airway resistance, leak volume, airway pressure, and oxygen reserve index, were recorded at different time points: before LRM, immediately after LRM, and at 5, 15, and 30 minutes after LRM, as well as at the end of the surgery. The primary outcome was to assess an improvement in lung compliance. Dynamic lung compliance (mean ± SD) was significantly increased from 49.2 ± 1.8 to 70.15 ± 3.2 mL/cmH2O (P < .05) after LRM. Static lung compliance (mean ± SD) was increased considerably from 52.4 ± 1.7 to 65.0 ± 2.5 mL/cmH2O (P < .05) after the LRM. Both parameters maintained a statistically significant increased status for a certain period compared to baseline despite a decreased degree of increment. Airway resistance (mean ± SD) was significantly reduced after the LRM from 12.05 ± 0.56 to 10.41 ± 0.64 L/cmH2O/s (P < .05). Stepwise LRM using i-gel may improve lung compliance and airway resistance. Repeated procedures could lead to prolonged improvements in respiratory parameters.
Topics: Humans; Middle Aged; Prospective Studies; Male; Female; Aged; Lung Compliance; Adult; Airway Resistance; Positive-Pressure Respiration
PubMed: 38941413
DOI: 10.1097/MD.0000000000038718 -
Medicine Jun 2024To investigate whether intravenous administration of tranexamic acid (TXA) prior to arthroscopic rotator cuff repair improves operative blood loss, postoperative... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
To investigate whether intravenous administration of tranexamic acid (TXA) prior to arthroscopic rotator cuff repair improves operative blood loss, postoperative fibrinolytic index, inflammatory response, and postoperative pain.
METHODS
This was a prospective, double-blind, randomized controlled study. From January 2023 to February 2024, 64 patients who required arthroscopic rotator cuff repair were included and divided into tranexamic acid group (T group) group and control group (C group) according to the random number table method. In T group, 1000 mg TXA was administered intravenously 10 minutes before surgery, and an equivalent dose of normal saline was administered intravenously 10 minutes before surgery in C group. Intraoperative bleeding, postoperative fibrinolytic indexes, inflammatory indexes, pain scores, and occurrence of adverse effects were compared between the 2 groups.
RESULTS
Intraoperative bleeding in T group was lower than that in C group (P < .05); D-D and FDP in T group were significantly lower than those in C group (P < .05); postoperative TNF-α and IL-6 in 2 groups was higher than that before operation and T group was lower than C group (P < .05); The pain scores of the 2 groups after operation were lower than those before operation (P < .05), and there was no difference between the 2 groups (P > .05).
CONCLUSION SUBSECTIONS
TXA is able to reduce blood loss and inflammatory reactions, modulate fibrinolytic function, and promote postoperative recovery in patients undergoing arthroscopic rotator cuff repair, with no elevated risk of complications.
Topics: Humans; Tranexamic Acid; Male; Female; Antifibrinolytic Agents; Double-Blind Method; Middle Aged; Arthroscopy; Prospective Studies; Rotator Cuff Injuries; Blood Loss, Surgical; Pain, Postoperative; Aged; Adult; Administration, Intravenous
PubMed: 38941391
DOI: 10.1097/MD.0000000000038515