Parecoxib expresses anti-metastasis effect through inhibition of epithelial-mesenchymal transition and the Wnt/ß-catenin signaling pathway in human colon cancer DLD-1 cell line.

Colorectal cancer is the third leading cause of cancer death in Taiwan. Current treatments involve combination of surgical resection, radiation, and chemotherapy. These treatments have demonstrated to increased five-year survival of a patient with colorectal cancer. However, metastasis is a major capability of cancer cells that causes poor prognosis, recurrence, and even death. Epidemiological and clinical studies have suggested the use of non-steroidal anti-inflammatory drugs (NSAIDs) as an effective class of compounds to prevent colon cancer. Parecoxib is an NSAID and the only parenterally administered selective cyclooxygenase (COX)-2 inhibitor. In this study, we evaluated whether parecoxib inhibits the metastasis of DLD-1 human colon cancer cells, a COX-2 null cell line, and the underlying mechanism. Cell migration of the DLD-1 cells was significantly inhibited by parecoxib treatment as shown by the Transwell migration assay. This enhanced anti-migration effect was correlated with the attenuated phosphorylation of Akt, expression of vimentin (a mesenchymal marker), and ß-catenin, and corresponded with the upregulated GSK3ß and E-cadherin (an epithelial marker). These findings suggested that parecoxib could inhibit the epithelial-mesenchymal transition (EMT) and metastasis in human colon cancer cells by downregulating ß-catenin. Thus, parecoxib could provide a novel prospective strategy for a combination treatment with chemotherapeutic drugs against metastasis of human colon cancer.

Acute and chronic bilateral internal carotid artery occlusion.

PURPOSE: Occlusion of both internal carotid arteries (ICAs) is rare. Clinical manifestations of stroke vary widely. We conducted a retrospective review to compare acute and chronic bilateral ICA occlusion. METHODS: We retrospectively reviewed records of inpatients with acute ischemic stroke and carotid duplex sonography (CDS) during the period from February 2006 to February 2021. RESULTS: Bilateral ICA occlusion and acute bilateral ICA occlusion accounted for 0.3% and less than 0.1% of all ischemic stroke cases, respectively. All five patients with acute bilateral ICA occlusion presented with consciousness disturbance. Three patients died within 1 week, and two patients had a vegetative outcome. Pituitary apoplexy with bilateral ICA occlusion was observed in one patient. Forward bilateral ophthalmic arterial flow (OAF) was detected in all three patients who received CDS. Among 13 patients with chronic bilateral ICA occlusion, five and six had modified Rankin Scale (mRS) scores upon discharge of more than 5 and less than 2, respectively; two patients did not have a stroke. Of the 13 patients, 11 had reversed bilateral OAF. Patients with acute bilateral ICA occlusion had a higher rate of initial consciousness disturbance, Glasgow Coma Scale score of less than 9, National Institute of Health Stroke Scale score of more than 20, and mRS score of more than 5. than that of patients with chronic bilateral ICA occlusion. CONCLUSION: Patients with acute bilateral ICA occlusion had higher initial stoke severity, poorer collateral circulation, and worse clinical outcomes than did those with chronic bilateral ICA occlusion. Physicians must pay attention to rare causes of acute bilateral ICA occlusion, including pituitary apoplexy.

Increased glutathione contributes to stress tolerance and global translational changes in Arabidopsis.

Although glutathione is well known for its reactive oxygen species (ROS) scavenging function and plays a protective role in biotic stress, its regulatory function in abiotic stress still remains to be elucidated. Our previous study showed that exogenously applied reduced glutathione (GSH) could improve abiotic stress tolerance in Arabidopsis. Here, we report that endogenously increased GSH also conferred tolerance to drought and salt stress in Arabidopsis. Moreover, both exogenous and endogenous GSH delayed senescence and flowering time. Polysomal profiling results showed that global translation was enhanced after GSH treatment and by the induced increase of GSH level by salt stress. By performing transcriptomic analyses of steady-state and polysome-bound mRNAs in GSH-treated plants, we reveal that GSH has a substantial impact on translation. Translational changes induced by GSH treatment target numerous hormones and stress signaling molecules, which might contribute to the enhanced stress tolerance in GSH-treated plants. Our translatome analysis also revealed that abscisic acid (ABA), auxin and jasmonic acid (JA) biosynthesis, as well as signaling genes, were activated during GSH treatment, which has not been reported in previously published transcriptomic data. Together, our data suggest that the increased glutathione level results in stress tolerance and global translational changes.

Seasonal Variations in Stroke and a Comparison of the Predictors of Unfavorable Outcomes among Patients with Acute Ischemic Stroke and Cardioembolic Stroke.

We investigated the seasonal variations in stroke in 4040 retrospectively enrolled patients with acute ischemic stroke (AIS) admitted between January 2011 and December 2022, particularly those with cardioembolic (CE) stroke, and compared predictors of unfavorable outcomes between AIS patients and CE stroke patients. The classification of stroke subtypes was based on the Trial of ORG 10172 in Acute Stroke Treatment. Stroke occurrence was stratified by seasons and weekdays or holidays. Of all AIS cases, 18% were of CE stroke. Of all five ischemic stroke subtypes, CE stroke patients were the oldest; received the most thrombolysis and thrombectomy; had the highest initial National Institutes of Stroke Scale (NIHSS) and discharge modified Rankin Scale (mRS) scores; and had the highest rate of in-hospital complications, unfavorable outcomes (mRS > 2), and mortality. The highest CE stroke prevalence was noted in patients aged ≥ 85 years (30.9%); moreover, CE stroke prevalence increased from 14.9% in summer to 23.0% in winter. The main predictors of death in patients with CE stroke were age > 86 years, heart rate > 79 beats/min, initial NIHSS score > 16, neutrophil-to-lymphocyte ratio (NLR) > 6.4, glucose > 159 mg/dL, cancer history, in-hospital complications, and neurological deterioration (ND). The three most dominant factors influencing death, noted in not only patients with AIS but also those with CE stroke, are high initial NIHSS score, ND, and high NLR. We selected the most significant factors to establish nomograms for predicting fatal outcomes. Effective heart rhythm monitoring, particularly in older patients and during winter, may help develop stroke prevention strategies and facilitate early AF detection.

Parecoxib and 5-Fluorouracil Synergistically Inhibit EMT and Subsequent Metastasis in Colorectal Cancer by Targeting PI3K/Akt/NF-κB Signaling.

Colorectal cancer is one of the most common causes of cancer mortality worldwide, and innovative drugs for the treatment of colorectal cancer are continually being developed. 5-Fluorouracil (5-FU) is a common clinical chemotherapeutic drug. Acquired resistance to 5-FU is a clinical challenge in colorectal cancer treatment. Parecoxib is a selective COX-2-specific inhibitor that was demonstrated to inhibit metastasis in colorectal cancers in our previous study. This study aimed to investigate the synergistic antimetastatic activities of parecoxib to 5-FU in human colorectal cancer cells and determine the underlying mechanisms. Parecoxib and 5-FU synergistically suppressed metastasis in colorectal cancer cells. Treatment with the parecoxib/5-FU combination induced an increase in E-cadherin and decrease in ß-catenin expression. The parecoxib/5-FU combination inhibited MMP-9 activity, and the NF-κB pathway was suppressed as well. Mechanistic analysis denoted that the parecoxib/5-FU combination hindered the essential molecules of the PI3K/Akt route to obstruct metastatic colorectal cancer. Furthermore, the parecoxib/5-FU combination could inhibit reactive oxygen species. Our work showed the antimetastatic capacity of the parecoxib/5-FU combination for treating colorectal cancers via the targeting of the PI3K/Akt/NF-κB pathway.

Parecoxib Enhances Resveratrol against Human Colorectal Cancer Cells through Akt and TXNDC5 Inhibition and MAPK Regulation.

In this study, we discovered the mechanisms underlying parecoxib and resveratrol combination's anti-cancer characteristics against human colorectal cancer DLD-1 cells. We studied its anti-proliferation and apoptosis-provoking effect by utilizing cell viability 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, fluorescence microscope, gene overexpression, Western blot, and flow cytometry analyses. Parecoxib enhanced the ability of resveratrol to inhibit cell viability and increase apoptosis. Parecoxib in combination with resveratrol strongly enhanced apoptosis by inhibiting the expression of thioredoxin domain containing 5 (TXNDC5) and Akt phosphorylation. Parecoxib enhanced resveratrol-provoked c-Jun N-terminal kinase (JNK) and p38 phosphorylation. Overexpression of TXNDC5 and repression of JNK and p38 pathways significantly reversed the inhibition of cell viability and stimulation of apoptosis by the parecoxib/resveratrol combination. This study presents evidence that parecoxib enhances the anti-cancer power of resveratrol in DLD-1 colorectal cancer cells via the inhibition of TXNDC5 and Akt signaling and enhancement of JNK/p38 MAPK pathways. Parecoxib may be provided as an efficient drug to sensitize colorectal cancer by resveratrol.

Validity and Reliability of Point-of-Care Ultrasound for Detecting Moderate- or High-Grade Carotid Atherosclerosis in an Outpatient Department.

The prevalence of carotid stenosis is considerably higher in asymptomatic individuals with multiple risk factors than in the general population. We investigated the validity and reliability of carotid point-of-care ultrasound (POCUS) for rapid carotid atherosclerosis screening. We prospectively enrolled asymptomatic individuals with carotid risk scores of ≥7 who underwent outpatient carotid POCUS and laboratory carotid sonography. Their simplified carotid plaque scores (sCPSs) and Handa's carotid plaque scores (hCPSs) were compared. Of 60 patients (median age, 81.9 years), 50% were diagnosed as having moderate- or high-grade carotid atherosclerosis. The overestimation and underestimation of outpatient sCPSs were more likely in patients with low and high laboratory-derived sCPSs, respectively. Bland-Altman plots indicated that the mean differences between the participants' outpatients and laboratory sCPSs were within two standard deviations of their laboratory sCPSs. A Spearman's rank correlation coefficient revealed a strong positive linear correlation between outpatient and laboratory sCPSs (r = 0.956, p < 0.001). An intraclass correlation coefficient analysis indicated excellent reliability between the two methods (0.954). Both carotid risk score and sCPS were positively and linearly correlated with laboratory hCPS. Our findings indicate that POCUS has satisfactory agreement, strong correlation, and excellent reliability with laboratory carotid sonography, making it suitable for rapid screening of carotid atherosclerosis in high-risk patients.

Comparative Effectiveness of Two Models of Point-of-Care Ultrasound for Detection of Post-Void Residual Urine during Acute Ischemic Stroke: Preliminary Findings of Real-World Clinical Application.

We conducted a comparative study of two models of point-of-care ultrasound devices for measuring post-void residual urine (PVRU). We prospectively enrolled 55 stroke inpatients who underwent both real-time B-mode ultrasound (Device A) and automated three-dimensional (3D) scanning ultrasound (Device B), with a total of 108 measurements. The median PVRU volume of Device B was 40 mL larger than that of Device A. The PVRU difference between the devices was positively and linearly correlated with PVRU. The correlation of PVRU volume between the devices was strong, but the agreement level was only moderate. Measurement deviations were observed in 43 (40%) and 11 (10%) measurements with Device B and Device A, respectively. The PVRU volume was low in spherical bladder shapes but sequentially increased in triangular, undefined, ellipsoid, and cuboid bladder shapes. Further comparison of 60 sets of PVRU without measurement deviations revealed higher agreements between the devices at correction coefficients of 0.52, 0.66, and 0.81 for PVRU volumes of <100, 100-200, and >200 mL, respectively. The automated 3D scanning ultrasound is more convenient for learning and scanning, but it exhibits larger measurement deviations. Real-time B-mode ultrasound accurately visualizes the urinary bladder but tends to underestimate the urinary bladder when the PVRU volume is large. Hence, real-time B-mode ultrasound with automated PVRU-based adjustment of calculation formulas may be a better solution for estimating bladder volume.

Comparison of Clinical Features, Immune-Inflammatory Markers, and Outcomes Between Patients with Acute In-Hospital and Out-of-Hospital Ischemic Stroke.

PURPOSE: We investigated the differences of clinical features, four immune-inflammatory markers, namely neutrophil counts, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), as well as outcomes between patients with in-hospital ischemic stroke (IHIS) and out-of-hospital ischemic stroke (OHIS). PATIENTS AND METHODS: We retrospectively enrolled 72 patients with IHIS and 3330 patients with OHIS. RESULTS: IHIS accounted for 2% of all patients with ischemic stroke and occurred more often in cardiology and orthopedic surgery wards. Infection, cardiac disease, and pulmonary disorder were the most common causes of hospitalization. Compared with those with OHIS, patients with IHIS had higher levels of immune-inflammatory markers, initial National Institute of Health Stroke Scale (NIHSS) scores, longer hospital stays, higher rates of heart disease, large-artery atherosclerosis or cardioembolism, received more intravenous thrombolysis (IVT) or endovascular thrombectomies (EVTs), more complications, unfavorable outcomes, and mortality. Every immune-inflammatory marker exhibited positive correlations with initial NIHSS scores and discharge modified Rankin Scale scores among patients with OHIS. NLR and SII were higher among patients with a fatal outcome in both groups. Among patients receiving IVT, most of treatment time intervals were shorter for those with IHIS than those with OHIS. Significant factors for mortality were NLR >5.5, atrial fibrillation, and complications, with a C-statistic of 0.897 in those with IHIS; in those with OHIS, these factors were an initial NIHSS score of >10, NLR >6.0, atrial fibrillation, prior stroke, cancer history, and complications with a C-statistic of 0.902. The results were similar after replacing the NLR with SII. CONCLUSION: Patients with IHIS had more complicated clinical features, higher levels of immune-inflammatory markers, and higher rates of mortality than patients with OHIS. The most significant predictor for mortality among those with OHIS was NIHSS score >10, and the predictors among patients with IHIS were NLR >5.5 and SII >2120.

Effects of Heart Rate Variability Biofeedback in Patients With Acute Ischemic Stroke: A Randomized Controlled Trial.

BACKGROUND: Autonomic dysfunction, cognitive impairment, and psychological distress are associated with poorer prognosis in patients with acute ischemic stroke (AIS). Heart rate variability (HRV) biofeedback (BF) improves autonomic dysfunction, cognitive impairment, and psychological distress in other patient populations, but its effect in patients with AIS is still unclear. OBJECTIVE: This study investigated the effects of an HRVBF intervention on autonomic function, cognitive impairment, and psychological distress in patients with AIS. METHOD: In this randomized, controlled, single-blind trial, patients with AIS were randomly assigned to the experimental or control group. The experimental group received four HRVBF training sessions. The control group received usual care. Repeated measures of HRV, mini-mental status examination (MMSE), and Hospital Anxiety and Depression Scales (HADS) were collected prior to and at 1 and 3 months postintervention. RESULTS: A total of 35 patients completed the study (19 experimental, 16 control). HRV and HADS significantly improved in the experimental group (p < .001) but not in the control group. Likewise, only the experimental group showed significant improvements in HRV, MMSE, and HADS over time (p < .05). CONCLUSION: HRVBF is a promising intervention for improving autonomic function, cognitive impairment, and psychological distress in patients with AIS. More studies of HRVBF interventions are needed to further optimize the effects of HRVBF on autonomic, cognitive, and psychological function in patients with AIS.

PARO robot affects diverse interaction modalities in group sensory therapy for older adults with dementia.

We evaluated the seal-like robot PARO in the context of multi-sensory behavioral therapy in a local nursing home. Participants were 10 elderly nursing home residents with varying levels of dementia. We report three principle findings from our observations of interactions between the residents, PARO, and a therapist during seven weekly therapy sessions. Firstly, we show PARO provides indirect benefits for users by increasing their activity in particular modalities of social interaction, including visual, verbal, and physical interaction, which vary between primary and non-primary interactors. Secondly, PARO's positive effects on older adults' activity levels show steady growth over the duration of our study, suggesting they are not due to short-term "novelty effects." Finally, we show a variety of ways in which individual participants interacted with PARO and relate this to the "interpretive flexibility" of its design.

Successful management of severe upper airway obstruction during emergence of anesthesia in consequence of fracture of deflated laryngeal mask airway due to biting--a case report.

Biting the laryngeal mask airway during general anesthesia in the absence of a bite block as a forestallment is a common but usually uncomplicated event. We report a young healthy adult female patient who underwent removal of fixation implant in the right elbow under general anesthesia, during the emergence of which she bit and severed the airway tube of the laryngeal mask airway (LMA) after cuff deflation and developed upper airway obstruction in consequence of air blockade by the displaced deflated LMA cuff remaining inside the mouth. Removal of residual part of the LMA in the mouth was successful with propofol re-anesthetization without molestation of 02 saturation. We discuss the management of this critical airway condition resulting from fracture of deflated LMA in the closed mouth.

Comparison of intravenous patient-controlled analgesia with buprenorphine versus morphine after lumbar spinal fusion--a prospective randomized clinical trial.

BACKGROUND: Opioid-based patient-controlled analgesia (PCA) has been used widely and effectively after spine surgery. The untoward effects of intravenous opioids could vary with the drug and dose applied. Buprenorphine, a partial opioid agonist, might be devoid of the adverse effects which the traditional opioids have. We conducted this prospective randomized clinical trial to evaluate the efficacy and safety of buprenorphine for intravenous PCA after spine surgery. METHODS: Fifty patients undergoing elective lumbar spinal fusion were randomly assigned to either buprenorphine or morphine group. PCA was administered in a double-blind manner for a 2-day postoperative course. The evaluation was initiated after patients were transferred to the post-anesthetic care unit. Pain assessment with visual analog scale (VAS) at rest and after pain elicitation by sitting was carried out and recorded at 6, 24, 48 hrs after surgery. Untoward effects were also collected. RESULTS: Twenty-five patients were randomized to each group. One patient in the buprenorphine group dropped out from the study due to dizziness. There was no difference between the groups with respect to the baseline variables. The VAS scores at rest and after elicitation of pain by sitting showed no difference between both groups. The delivered volume of buprenorphine, the numbers of demand and delivery, and the demand/delivery ratio were higher in buprenorphine than morphine group at 6 hr after surgery but were not different later. No major complications occurred in both groups. The pruritus incidence in buprenorphine group was significantly lower than in morphine group (0 vs. 24%, P = 0.02). Other adverse effects were similar in both groups. CONCLUSIONS: Both buprenorphine and morphine by intravenous PCA provided adequate pain relief after posterior lumbar spinal fusion. The incidences of side effects were similar in both groups except for pruritus which did not appear in buprenorphine group. Buprenorphine was as efficient as morphine and safe for intravenous PCA after spine surgery.