2,119 research outputs found

    Interrelationship of Stress, Environment, and Herpes Simplex Virus Type-1 on Behçet’s Disease: Using a Mouse Model

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    The purpose of this study was to investigate effects of stress and environment factors on the induction of Behçet’s disease (BD) using HSV-1 infected mouse model. BD is a chronic multisystemic inflammatory disease of unknown etiology. Environmental factors, immune dysfunction, and herpes simplex virus type-1 (HSV) infection might be triggers of BD. To investigate effects of environmental factors on the incidence of BD, HSV was inoculated into mice. Mice were then maintained in conventional facility or SPF facility to compare BD incidence rates. The incidence of BD was also tracked by adding stressors such as substance P (anxiety stress), 4°C (cold stress), xanthine sodium salt (oxidative stress), or 77 dB noise (noise stress). To clarify immune mechanisms involved in the difference in BD incidence caused by various stresses, dendritic cell activation markers were analyzed using flow cytometry. The combination of conventional environment, noise stress, and HSV had the highest rate of BD (38.1%) among all groups. However, HSV inoculated group in a SPF environment had the lowest incidence (2.2%). Frequencies of dendritic cell activation markers such as CD40, CD83, CD80, and CD86 were expressed differently under various stresses. Noise stress increased frequencies of CD83 positive cells. Noise stress also upregulated transcription factors T-bet and ROR-γt. Different gut microbiota compositions were observed between SPF and conventional environment by 16S rRNA sequence analysis. Environment and stress influenced the incidence of HSV-induced BD. Microbial diversity due to environmental differences might be one explanation for regional differences in the incidence of BD

    Refining oxygen management through rigorous Oxygen Reserve Index (ORi) monitoring in patients undergoing general anesthesia: a randomized controlled trial: ORi to avoid excessive hyperoxia

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    Optimizing oxygenation for patients necessitates a delicate balance between sufficient oxygen delivery and mitigating the potential hazards of hyperoxemia. We hypothesized that integrating Oxygen Reserve Index (ORi) monitoring would effectively reduce intraoperative hyperoxemia compared to reliance solely on pulse oximetry. This single-center randomized controlled trial included multiple trauma patients with ASA class 3 or higher undergoing general anesthesia. FiO(2) adjustments to 0.5 started at T0 with arterial blood gas analysis (ABGA) every 30-minutes. Patients were randomized into Group O (ORi monitoring) and Group N (pulse oximetry). In Group O, FiO(2) was reduced if ORi > 0.05; unchanged if ORi was 0-0.05. Group N decreased FiO(2) if SpO(2) was 100%, unchanged if SpO(2) was < 99%, and increased FiO(2) by 0.05 until SpO(2) reached 95% or above. 54 participants were randomized, and 51 analyzed. Group O demonstrated a significantly higher percentage of normoxemia (80 /= 120mmHg and >/= 150mmHg at 0.06 and 0.22, respectively. Simultaneous ORi and pulse oximetry reduce intraoperative hyperoxemia through safe and meticulous protocol adherence in patients

    Immunomodulatory Effects of a Probiotic Mixture: Alleviating Colitis in a Mouse Model through Modulation of Cell Activation Markers and the Gut Microbiota

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    Ulcerative colitis (UC) is a persistent inflammatory intestinal disease that consistently affects the colon and rectum. Its exact cause remains unknown. UC causes a considerable challenge in healthcare, prompting research for novel therapeutic strategies. Although probiotics have gained popularity as possible candidates for managing UC, studies are still ongoing to identify the best probiotics or probiotic mixtures for clinical applications. This study aimed to determine the efficacy of a multi-strain probiotic mixture in mitigating intestinal inflammation in a colitis mouse model induced by dextran sulfate sodium. Specifically, a multi-strain probiotic mixture consisting of Tetragenococcus halophilus and Eubacterium rectale was used to study its impact on colitis symptoms. Anti-inflammatory effects were evaluated using ELISA and flow cytometry. The configuration of gut microbial communities was determined using 16S rRNA metagenomic analysis. According to this study, colitis mice treated with the probiotic mixture experienced reduced weight loss and significantly less colonic shortening compared to untreated mice. Additionally, the treated mice exhibited increased levels of forkhead box P3 (Foxp3) and interleukin 10, along with decreased expression of dendritic cell activation markers, such as CD40+, CD80+, and CD83+, in peripheral blood leukocytes and intraepithelial lymphocytes. Furthermore, there was a significant decrease in the frequencies of CD8+N.K1.1+ cells and CD11b+Ly6G+ cells. In terms of the gut microbiota, probiotic-mixture treatment of colitis mice significantly increased the abundance of the phyla Actinobacteria and Verrucomicrobia (p < 0.05). These results provide valuable insights into the therapeutic promise of multi-strain probiotics, shedding light on their potential to alleviate colitis symptoms. This research contributes to the ongoing exploration of effective probiotic interventions for managing inflammatory bowel disease

    Magnesium Sulfate and Cerebral Oxygen Saturation in Mild Traumatic Brain Injury: A Randomized, Double-Blind, Controlled Trial

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    Perioperative cerebral hypoperfusion/ischemia is considered to play a pivotal role in the development of secondary traumatic brain injury (TBI). This prospective randomized, double-blind, controlled study investigated whether magnesium sulfate (MgSO(4)) infusion was associated with neuroprotection in maintaining regional cerebral oxygen saturation (rSO(2)) values in patients with mild TBI undergoing general anesthesia. Immediately after intubation, we randomly assigned patients with TBI to receive either intravenous MgSO(4) (30 mg/kg for 10 min, followed by a continuous infusion of 15 mg/kg/h) or a placebo (saline) during surgery. We also implemented an intervention protocol for a sudden desaturation exceeding 20% of the initial baseline rSO(2). The intraoperative rSO(2) values were similar with respect to the median (left. 67% vs. 66%, respectively; p = 0.654), lowest, and highest rSO(2) in both groups. The incidence (left 31.2% vs. 24.3%; p = 0.521) and duration (left 2.6% vs. 3.5%; p = 0.638) of cerebral desaturations (the relative decline in rSO(2) < 80% of the baseline value) were also similar for both groups. Although the patients suffered serious traumatic injuries, all critical desaturation events were restored (100%) following stringent adherence to the intervention protocol. Intraoperative remifentanil consumption, postoperative pain intensity, and fentanyl consumption at 6 h were lower in the MgSO(4) group (p = 0.024, 0.017, and 0.041, respectively) compared to the control group, whereas the satisfaction score was higher in the MgSO(4) group (p = 0.007). The rSO(2) did not respond to intraoperative MgSO(4) in mild TBI. Nevertheless, MgSO(4) helped the postoperative pain intensity, reduce the amount of intraoperative and postoperative analgesics administered, and heighten the satisfaction score

    Magnesium Sulfate Enables Patient Immobilization during Moderate Block and Ameliorates the Pain and Analgesic Requirements in Spine Surgery, Which Can Not Be Achieved with Opioid-Only Protocol: A Randomized Double-Blind Placebo-Controlled Study

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    Spine surgery is painful despite the balanced techniques including intraoperative and postoperative opioids use. We investigated the effect of intraoperative magnesium sulfate (MgSO4) on acute pain intensity, analgesic consumption and intraoperative neurophysiological monitoring (IOM) during spine surgery. Seventy-two patients were randomly allocated to two groups: the Mg group or the control group. The pain intensity was significantly alleviated in the Mg group at 24 h (3.2 ± 1.7 vs. 4.4 ± 1.8, p = 0.009) and 48 h (3.0 ± 1.2 vs. 3.8 ± 1.6, p = 0.018) after surgery compared to the control group. Total opioid consumption was reduced by 30% in the Mg group during the same period (p = 0.024 and 0.038, respectively). Patients in the Mg group required less additional doses of rocuronium (0 vs. 6 doses, p = 0.025). Adequate IOM recordings were successfully obtained for all patients, and abnormal IOM results denoting warning criteria (amplitude decrement >50%) were similar. Total intravenous anesthesia with MgSO4 combined with opioid-based conventional pain control enables intraoperative patient immobilization without the need for additional neuromuscular blocking drugs and reduces pain intensity and analgesic requirements for 48 h after spine surgery, which is not achieved with only opioid-based protocol

    Tartaric Acid Exacerbates DSS-Induced Colitis by Promoting Eosinophilic Inflammation via IL-13 and IL-5Rα Upregulation

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    Eosinophils are granulocytes involved in the effector phase of type 2 T cell immune responses, which are elevated in inflammatory conditions like ulcerative colitis (UC) and other allergic diseases. UC is a chronic inflammatory colon disease, marked by excessive eosinophil infiltration and elevated Th2 cytokines, which contribute to mucosal inflammation and tissue damage. Dietary factors, including certain organic acids, can influence UC progression by modulating gut immune responses. This research is the first to explore the dose-dependent effects of tartaric acid (TA), a naturally occurring organic acid widely used in the food industry, on eosinophil activation and Th2 cytokine response in both normal mice and a dextran sulfate sodium (DSS)-induced colitis model. Normal mice were treated with TA at varying doses (5 µg, 25 µg, and 50 µg/mouse/day), while colitis mice received 50 µg TA. Eosinophil activation markers (CD11b+, SiglecF+, and CCR3+), Th2 cytokines (IL-4, IL-13, and IL-31), and IL-17 were assessed in peripheral blood leukocytes, lymph nodes, and splenocytes using flow cytometry. Additionally, mRNA expression levels of eosinophil-associated chemokines and cytokines in the splenocytes were quantified with real-time qPCR. Our results demonstrate a dose-dependent effect of TA, with the highest dose (50 µg) significantly increasing eosinophil activation markers, Th2 cytokines, IL-17, and mRNA expression of SiglecF, CCL11, and toll-like receptor 4 in normal mice. In colitis mice, treatment with 50 µg TA showed marked increases in IL-13 levels compared to those of untreated colitis mice, reflecting increased eosinophil recruitment to inflamed tissues. Moreover, mRNA expression of IL-5Rα was elevated in normal mice and colitis mice administered with TA. These results suggest that TA enhances eosinophil proliferation, the upregulation of their regulatory molecules, and Th2 immune profiles, potentially worsening the severity of colitis

    Tetragenococcus halophilus Alleviates Intestinal Inflammation in Mice by Altering Gut Microbiota and Regulating Dendritic Cell Activation via CD83

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    Ulcerative colitis (UC) is one of the major subtypes of inflammatory bowel disease with unknown etiology. Probiotics have recently been introduced as a treatment for UC. Tetragenococcus halophilus (T. halophilus) is a lactic acid-producing bacterium that survives in environments with high salt concentrations, though little is known about its immunomodulatory function as a probiotic. The purpose of this study is to determine whether T. halophilus exerts an anti-inflammatory effect on intestinal inflammation in mice. Colitis was induced in C57BL/6J mice by feeding 4% DSS in drinking water for 7 days. T. halophilus was orally administered with DSS. Anti-inflammatory functions were subsequently evaluated by flow cytometry, qRT-PCT, and ELISA. Gut microbial composition was analyzed by 16S rRNA metagenomic analysis. DSS-induced colitis mice treated with T. halophilus showed less weight loss and significantly suppressed colonic shortening compared to DSS-induced colitis mice. T. halophilus significantly reduced the frequency of the dendritic cell activation molecule CD83 in peripheral blood leukocytes and intestinal epithelial lymphocytes. Frequencies of CD8+NK1.1+ cells decreased in mice with colitis after T. halophilus treatment and IL-1β levels were also reduced. Alteration of gut microbiota was observed in mice with colitis after administration of T. halophilus. These results suggest T. halophilus is effective in alleviating DSS-induced colitis in mice by altering immune regulation and gut microbiome compositions

    Immediate retrograde amnesia induced by midazolam: A prospective, non-randomised cohort study

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    Background: Midazolam, a short-acting benzodiazepine, has sedative, anxiolytic, amnestic and anticonvulsant effects. Given its advantages of rapid onset, short duration and low toxicity, midazolam is optimal for any procedural sedation. Midazolam is known to cause anterograde amnesia; however, the possibility of retrograde amnesia has also been raised. This prospective cohort, non-randomised study evaluated the presence and extent of retrograde amnesia induced by midazolam during caesarean delivery. Methods: One hundred parturients scheduled for elective caesarean delivery under spinal anaesthesia were enrolled. As soon as giving birth, six picture cards were shown to the patients in 1-min intervals, and then midazolam (0.1 mg/kg) was given or not according to the patients’ preference. This overall retrograde recall rate of six cards was the primary outcome of our study, which was asked by a blinded investigator. Results: The overall retrograde card recall rate was lower in the midazolam group compared with the control group (77.0 ± 13.4 vs. 87.7 ± 3.9%, P <.001), especially at 1 minute before midazolam administration (58% vs. 88%, P <.001). Decreased memory trend was observed as time progressed towards midazolam administration in the midazolam group (P =.035). More patients answered ‘yes’ to the factitious event in the midazolam group than in the control group (26% vs. 4%, P =.004). Conclusion: Intravenous midazolam could cause a brief-period retrograde amnesia in visual and event memory. Moreover, there were more spurious reports of intraoperative factitious events in the midazolam group, implying that episodic memories were also affected by midazolam

    Impact of ERAP1 downregulation on the pathogenesis of DSS-induced colitis and therapeutic response to sulfasalazine

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    INTRODUCTION: Ulcerative colitis (UC) is a life-threatening heterogeneous condition characterized by inflammation of the colon. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is essential for antigen processing and immune regulation, however, its specific role in UC pathogenesis and therapeutic response remains unclear. This study aimed to investigate the role of ERAP1 in the response to sulfasalazine, a standard treatment for UC, using an ERAP1-heterozygous (ERAP1(+/-)) mouse model susceptible to colitis. METHODS: Wild-type (WT) and ERAP1(+/-) mice were treated with 2.5% dextran sulfate sodium to induce colitis, followed by sulfasalazine administration. Colitis severity was assessed through histopathology. Immune cell populations, including neutrophils, dendritic cells, T cells, and NK1.1+ cells, were analyzed using flow cytometry. RNA sequencing of colonic tissues was performed to assess gene expression changes associated with reduced ERAP1 expression. RESULTS: ERAP1(+/-) mice exhibited mildly increased susceptibility to DSS-induced colitis, with greater weight loss and distinct alterations in immune cell infiltration compared to WT mice. These differences were further pronounced after sulfasalazine treatment. RNA sequencing identified 428 differentially expressed genes between ERAP1(+)/(-) and WT mice. Among these, 28 genes were previously associated with colitis or colorectal cancer, of which 11 were upregulated and 17 downregulated in ERAP1(+/-) mice. RT-qPCR confirmed significantly elevated expression of Anxa9, Atp2a1, and Hepacam2 in ERAP1(+/-) mice after sulfasalazine treatment, indicating a differential therapeutic response. CONCLUSION: Collectively, our findings show that partial ERAP1 deficiency promotes immune dysregulation, alters the expression of inflammation-associated genes, and impairs sulfasalazine efficacy. Therefore, ERAP1 may serve as a key regulator in the pathogenesis of UC and a potential target for therapy

    The Effect of Adjustment of Endotracheal Tube Cuff Pressure during Scarless Remote Access Endoscopic and Robotic Thyroidectomy on Laryngo-Pharyngeal Complications: Prospective Randomized and Controlled Trial

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    Scarless remote access endoscopic and robotic thyroidectomy has been recently performed as a safe and feasible method. However, little is known about the laryngo-pharyngeal complications after surgery and the effect of adjusting the endotracheal tube cuff pressure during surgery on laryngo-pharyngeal complications. Patients were randomized into two groups: the control group (n = 52) and adjusted group (n = 52). The initial cuff pressure was set to 25 mmHg and then monitored without adjustment (control group) or with adjustment at approximately 25 mmHg (adjusted group) throughout surgery. The incidences and severity of postoperative sore throat (POST), hoarseness, dysphagia, and cough were recorded at 1, 6, 24, and 48 h after surgery. Cuff pressures of the control group changed significantly over time and were higher than those of the adjusted group. The incidence of POST was lower in the adjusted group at 24 h postoperatively (p = 0.035), and there was a significant difference in the severity of POST at 6 and 24 h postoperatively between the two groups. There were no differences in the incidence of hoarseness, dysphagia, and cough between the two groups, except dysphagia and cough at 6 h postoperatively. Therefore, intraoperative monitoring and adjustment of the cuff pressure can reduce the incidence of laryngo-pharyngeal complications
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