Hyperuricemia exacerbates abdominal aortic aneurysm formation through the URAT1/ERK/MMP-9 signaling pathway.

OBJECTIVE: Previous studies have revealed associations between hyperuricemia and microvascular diseases, but the association between hyperuricemia and abdominal aortic aneurysm (AAA) remains unclear. The aim of this study was to elucidate the pathogenesis and prove the relationship between AAA and hyperuricemia. METHODS: A retrospective study was performed to validate the growth rates of AAA in humans with different serum uric acid levels. A murine model of angiotensin II-induced AAA was used to assess the effects of hyperuricemia on AAA growth in vivo, and human aortic smooth muscle cells (HASMCs) were used to study the pathways involved in these effects in vitro. RESULTS: We analyzed data from 107 AAA patients and found that patients with serum uric acid levels above 9 mg/dl had higher AAA growth rates than patients with serum uric acid levels between 4 and 7.9 mg/dl. In vivo, induction of hyperuricemia increased the incidence of AAA formation and the abdominal aortic diameter in mice. The hyperuricemic mice exhibited higher levels of urate transporter 1 (URAT1) expression, phospho-extracellular signal-regulated kinase (p-ERK)1/2 expression, reactive oxygen species (ROS) levels and matrix metalloproteinase (MMP)-9 expression in the abdominal aorta than the control mice. Soluble uric acid increased the expression of URAT1, p-ERK1/2, and MMP-9 and the levels of ROS in HASMCs in vitro. CONCLUSIONS: We have provided human evidence that hyperuricemia exacerbates AAA formation. In addition, our murine experimental evidence suggests that hyperuricemia exacerbates AAA formation and reveals that the URAT1/ERK1/2/ROS/MMP-9 pathway is among the pathways activated by uric acid in HASMCs.

The impact of smartphone use on learning effectiveness: A case study of primary school students.

This study investigated the effects of smartphone use on the perceived academic performance of elementary school students. Following the derivation of four hypotheses from the literature, descriptive analysis, t testing, one-way analysis of variance (ANOVA), Pearson correlation analysis, and one-way multivariate ANOVA (MANOVA) were performed to characterize the relationship between smartphone behavior and academic performance with regard to learning effectiveness. All coefficients were positive and significant, supporting all four hypotheses. We also used structural equation modeling (SEM) to determine whether smartphone behavior is a mediator of academic performance. The MANOVA results revealed that the students in the high smartphone use group academically outperformed those in the low smartphone use group. The results indicate that smartphone use constitutes a potential inequality in learning opportunities among elementary school students. Finally, in a discussion of whether smartphone behavior is a mediator of academic performance, it is proved that smartphone behavior is the mediating variable impacting academic performance. Fewer smartphone access opportunities may adversely affect learning effectiveness and academic performance. Elementary school teachers must be aware of this issue, especially during the ongoing COVID-19 pandemic. The findings serve as a reference for policymakers and educators on how smartphone use in learning activities affects academic performance.

Aldehyde dehydrogenase 2 protects against abdominal aortic aneurysm formation by reducing reactive oxygen species, vascular inflammation, and apoptosis of vascular smooth muscle cells.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is an enzyme that detoxifies aldehydes by converting them to carboxylic acids. ALDH2 deficiency is known to increase oxidative stress. Increased oxidative stress plays a pivotal role in abdominal aortic aneurysm (AAA) pathogenesis. Reactive oxygen species (ROS) promote degradation of the extracellular matrix (ECM) and vascular smooth muscle cell (VSMC) apoptosis. Reducing oxidative stress by an ALDH2 activator could have therapeutic potential for limiting AAA development. We hypothesized that ALDH2 deficiency could increase the risk for AAA by decreasing ROS elimination and that an ALDH2 activator could provide an alternative option for AAA treatment. The National Center for Biotechnology (NCBI) Gene Expression Omnibus (GEO) database was used. Human aortic smooth muscle cells (HASMCs) were used for the in vitro experiments. Gene-targeted ALDH2*2 KI knock-in mice on a C57BL/6J background and apolipoprotein E knockout (ApoE KO) mice were obtained. An animal model of AAA was constructed using osmotic minipumps to deliver 1000 ng/kg/min angiotensin II (AngII) for 28 days. Patients with AAA had significantly lower ALDH2 expression levels than normal subjects. ALDH2*2 KI mice were susceptible to AngII administration, exhibiting significantly increased AAA incidence rates and increased aortic diameters. Alda-1, an ALDH2 activator, reduced AngII-induced ROS production, NF-kB activation, and apoptosis in HASMCs. Alda-1 attenuated AngII-induced aneurysm formation and decreased aortic expansion in ApoE KO mice. We concluded that ALDH2 deficiency is associated with the development of AAAs in humans and a murine disease model. ALDH2 deficiency increases susceptibility to AngII-induced AAA formation by attenuating anti-ROS effects and increasing VSMC apoptosis and vascular inflammation. Alda-1 was shown to attenuate the progression of experimental AAA in a murine model.

Association between surgical repair of aortic aneurysms and the diagnosis of intracranial aneurysms.

OBJECTIVE: Aortic aneurysms (AAs) and intracranial aneurysms (IAs) share several clinical risk factors, a genetic predisposition, and molecular signaling pathways. Nonetheless, associations between IAs and AAs remain to be thoroughly validated in large-scale studies. In addition, no effective medical therapies exist for unruptured IAs or AAs. METHODS: Data for this nationwide, population-based, retrospective, cohort study described herein were obtained from the National Health Insurance Research Database in Taiwan. The study outcomes assessed were (1) the cumulative incidence of IAs, which was compared between AA and patients without an AA and (2) the cumulative incidence of IAs in patients with AAs during the 13-year follow-up period, which was further compared among those who underwent open surgical repair (OSR), endovascular aneurysm repair or nonsurgical treatment (NST). RESULTS: Our analyses included 20,280 patients with an AA and 20,280 propensity score-matched patients without an AA. Compared with the patients without an AA, patients with AA exhibited a significantly increased risk of an IA diagnosis (adjusted hazard ratio [HR], 3.395; P < .001). Furthermore, 6308 patients with AAs were treated with surgical intervention and another 6308 propensity score-matched patients with AAs were not. Patients with an AA who underwent OSR had a significantly lower risk of being diagnosed with an IA than patients with an AA who underwent endovascular aneurysm repair or NST (adjusted HR, 0.491 [P < .001] and adjusted HR, 0.473 [P < .001], respectively). CONCLUSIONS: We demonstrated an association between IAs and AAs, even after adjusting for several comorbidities. We also found that OSR was associated with fewer recognized IAs than NST.

Roles of the hypoximir microRNA-424/322 in acute hypoxia and hypoxia-induced pulmonary vascular leakage.

Acute mountain sickness (AMS) occurs in up to 25% of unacclimatized persons who ascend to 3000 m and can result in high-altitude pulmonary edema (HAPE). MicroRNAs (miRs) can regulate gene expression at the post-transcriptional level. Hypoxia selectively disrupts endothelial tight junction complexes through a hypoxia-inducible factor-1α (HIF-1α)-dependent mechanism. Though increased HIF-1α expression is associated with adaptation and protection from AMS development in the early stage of hypoxia, a downstream effector of HIF-1α, VEGF, can induce overzealous endothelial barrier dysfunction, increase vascular permeability, and ultimately result in HAPE and high-altitude cerebral edema. We hypothesized that the fine-tuning of downstream effectors by miRs is paramount for the preservation of endothelial barrier integrity and the prevention of vascular leakage. We found that several miRs were up-regulated in healthy volunteers who were subjected to a 3100-m height. By reviewing the literature and using online bioinformatics prediction software, we specifically selected miR-424 for further investigation because it can modulate both HIF-1α and VEGF. Hypoxia-induced miR-424 overexpression is HIF-1α dependent, and miR-424 stabilized HIF-1α, decreased VEGF expression, and promoted vascular endothelial cadherin phosphorylation. In addition, hypoxia resulted in endothelial barrier dysfunction with increased permeability; miR-424 thus attenuated hypoxia-induced endothelial cell senescence and apoptosis. miR-322 knockout mice were susceptible to hypoxia-induced pulmonary vascular leakage. miR-322 mimics improved hypoxia-induced pulmonary vascular leakage in vivo. We conclude that several miRs were up-regulated in healthy adult volunteers subjected to hypobaric hypoxemia. miR-424/322 could modulate the HIF-1α-VEGF axis and prevent hypoxia-induced pulmonary vascular leakage under hypoxic conditions.-Tsai, S.-H., Huang, P.-H., Tsai, H.-Y., Hsu, Y.-J., Chen, Y.-W., Wang, J.-C., Chen, Y.-H., Lin, S.-J. Roles of the hypoximir microRNA-424/322 in acute hypoxia and hypoxia-induced pulmonary vascular leakage.

A Population-Based Retrospective Analysis of Post-In-Hospital Cardiac Arrest Survival after Modification of the Chain of Survival.

BACKGROUND: In 2010, the American Heart Association recommended that postcardiac arrest care should be included in the chain of survival to reduce permanent neurological damage, improve quality of life, and reduce health care expenses of postcardiac arrest care. OBJECTIVES: To investigate post-in-hospital cardiac arrest (IHCA) survival prior to and after modification of the chain of survival in 2010, with subgroup analyses per age and concomitant coronary heart disease (CHD). METHODS: We retrospectively searched the National Health Insurance Research Database for the 2007-2015 period to collect case data coded as "427.41" or "427.5" per International Classification of Disease Clinical Modification, Ninth revision codes and analyzed the data with SPSS v22.0. RESULTS: The 1-day survival rate in the 2011-2015 period was 2% higher than that in the 2007-2010 period (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04). Moreover, in the 2011-2015 period, the survival-to-discharge rate was increased by 1% in patients under 65 years (OR 1.01, 95% CI 1.00-1.02) and 1% in CHD patients (OR 1.01, 95% CI 1.01-1.02) compared with that in the 2007-2010 period. CONCLUSION: For patients with IHCA, the overall short-term survival improved significantly after modification of the chain of survival. Younger patients and patients with CHD had better long-term survival.

Swollen and bloodshot eye following headache.

A ruptured cavernous carotid aneurysm (CCA) with carotid cavernous fistula can appear as a benign headache but progress to a swollen and bloodshot eye overnight. A 66-year-old woman visited emergency department with sudden onset of pain behind her left forehead and vomiting. She was treated for a migraine-like headache and discharged. She presented again on the next day with a persistent headache and a swollen left eye with blurred vision. An ophthalmologic examination revealed erythema of the left lid and chemosis at the temporal and lower bulbar conjunctiva. A cranial nonenhanced computed tomography (CT) scan had been performed at her previous visit. The scan exhibited a nodular mass lesion involving the left cavernous sinus. CT angiography was subsequently used to determine that the lesion was a giant aneurysm in the left cavernous internal carotid artery, causing enlargement of the left ophthalmic veins. The symptoms of her left eye rapidly progressed to severe chemosis, edematous change over periocular region, and limited movements after 8 h. The patient received emergent lateral canthotomy and inferior cantholysis to avoid acute orbital compartment syndrome and was subsequently treated with stent-assisted coil embolization. A ruptured CCA is an urgent condition that requires rapid assessment of both cranial vascular and ocular lesions. A history of sudden onset headache with a nonpainful acute unilateral red eye may serve as a clue to prompt additional diagnostic studies and ophthalmologist evaluation. Adequate radiological studies and early endovascular intervention can reduce the likelihood of permanent ocular injury and vision impairment.

Focused Ultrasound Assists in Diagnosis and Management of Difficult Airway in Ludwig's Angina.

Ludwig's angina is a rapidly progressive and life-threatening medical emergency. The mortality rate is about 8%. Management of the difficult airway in Ludwig's angina has been challenging for clinical physicians. We reported an otherwise healthy 49-year-old female, who visited our emergency department with progressive swelling of her chin, drooling, and dyspnea. Ludwig's angina with impending airway compromise was promptly identified. The precise anatomy of the distorted neck was accessed using ultrasound as an adjunct. Emergent tracheostomy was then established successfully within minutes. Physicians should consider using ultrasound as an adjunct to define anatomy before performing emergent surgical airways.

Association between Atrial Fibrillation and Aortic Aneurysms: A Population-Based Cohort Study.

OBJECTIVE: Atrial fibrillation (AF) is the most common form of sustained arrhythmia. Several molecular pathways associated with the pathogenesis of AF also participate in the initiation and progression of aortic aneurysm (AA). In this study, we aimed to evaluate potential associations between AA and AF. PATIENTS AND METHODS: The data for this nationwide population-based retrospective cohort study were obtained from Taiwan's National Health Insurance Research Database (NHIRD). All medical conditions for each case and the controls were categorized using the 9th revision of the International Classification of Diseases (ICD-9). Odds ratios and 95% confidence intervals for associations between AF and AA were estimated using Cox regression and adjusted for comorbidities. RESULTS: Our analyses included 116,225 AF cases and 116,225 propensity score-matched controls. Compared with the controls, the patients with AF exhibited a significantly increased risk of developing an AA (adjusted hazard ratio, HR 1.243, p < 0.001). Another cohort of 19,776 patients diagnosed with AA were identified, and 19,776 propensity score-matched patients were included as controls. Patients who had AA were also at an increased risk of developing AF (adjusted HR 1.187, p < 0.001). Heart failure (HF) was a common risk factor for both AA and AF. CONCLUSION: There are associations between AF and AA. HF is a mutual risk factor for the development of AF and AA.

Obstructive Sleep Apnoea and Aortic Aneurysm: A Nationwide Population-Based Retrospective Study.

OBJECTIVE: To determine whether patients with obstructive sleep apnoea (OSA) have an increased risk of aortic aneurysm (AA). METHODS: The data for the nationwide population-based retrospective cohort study described here were obtained from the Taiwan National Health Insurance Research Database (NHIRD). We selected adult patients who had been newly diagnosed as having OSA and were followed up between 2000 and 2010. We excluded patients who had been diagnosed as having AA before the date of the new OSA diagnosis. The control cohort consisted of individuals who had no OSA history. The patients and the control cohort were selected by 1: 4 matching according to the following baseline variables: sex, age, index year, and comorbidities. The outcome measure was AA diagnosis. RESULTS: In total, 31,274 patients diagnosed as having OSA were identified. Compared to patients without OSA, they had no significantly discrepant cumulative risk of developing AA in subsequent years (p from log-rank test = 0.442). We used the Cox proportional-hazards regression model, which found that only male sex, older age, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and coronary artery disease were independently associated with AA occurrence among subjects with an OSA diagnosis. OSA was not associated with AA development. On the other hand, in the subgroup of COPD, patients with OSA had a higher incidence of risk of AA than those without OSA. CONCLUSION: When compared to those without OSA, patients with OSA do not have an increased AA risk.

Fucoidan attenuates angiotensin II-induced abdominal aortic aneurysms through the inhibition of c-Jun N-terminal kinase and nuclear factor κB activation.

BACKGROUND: Rupture of abdominal aortic aneurysm (AAA) is one of the leading causes of sudden death among the elderly. Most incidental AAAs are below the threshold for intervention at the time of detection; however, there is no evidence that commonly used cardiovascular drugs have clinical beneficial effects on AAA progression. Therefore, in addition to current cardiovascular risk-reducing treatments, an adjunctive medical therapy targeting the regulation of extracellular matrix metabolism is still required in the clinical setting. Fucoidan is an extract of brown seaweed and a sulfated polysaccharide. Emerging evidence suggests that fucoidan has potential cardiovascular applications. Numerous investigations of fucoidan in diseases of the cardiovascular system have mainly focused on its pleiotropic anti-inflammatory effects. Specifically, fucoidan has been shown to have matrix metalloproteinase (MMP)-reducing effects in several studies. We aimed to evaluate the beneficial effect of fucoidan on aneurysmal growth in a murine model of aortic aneurysm and further provide a rationale for using fucoidan as a medical adjunctive therapy. METHODS: A murine model of angiotensin II (Ang II)-induced AAA was used to assess the therapeutic effects of fucoidan on AAA growth in vivo. The characteristics and quantification of AAAs were determined in situ. Human umbilical vein endothelial cells were used for studying the involved pathways in vitro. Western blotting was used to detect the involved signaling pathways both in vivo and in vitro. RESULTS: Treatment with fucoidan significantly reduced the incidence of AAA formation. Administration of fucoidan significantly attenuated Ang II-induced aortic expansion from 1.56 ± 0.76 mm to 1.09 ± 0.30 mm. Administration of fucoidan significantly suppressed MMP-2 and MMP-9 activities and reduced the grade of elastin degradation in vivo. In vitro, we found that fucoidan could ameliorate the Ang II-induced phosphorylation of c-Jun N-terminal kinase and nuclear factor κB p65, and it further reduced MMP and reactive oxygen species production. CONCLUSIONS: Fucoidan inhibits the progression of experimental AAA growth through the attenuation of proinflammatory nuclear factor κB and c-Jun N-terminal kinase activation. Fucoidan could be a potential medical adjunctive therapy for small AAAs.

Kinect-based real-time audiovisual feedback device improves CPR quality of lower-body-weight rescuers.

BACKGROUND: Chest compression (CC) quality is associated with rescuer posture and body weight. We designed a Kinect module-based real-time audiovisual feedback (AVF) device to investigate the relationship between rescuer posture, body weight, and CC quality. METHODS: A total of 100 healthcare professionals were enrolled as participants in this randomized trial. A Kinect-based sensor system was used to monitor the depth and rate of CC and provide further real-time feedback. All participants were asked to perform continuous CC on a manikin with and without feedback for 2min individually in either a kneeling or standing position. RESULTS: A kneeling posture can provide higher rate of CC than a standing posture can (111.4±22.6 per minute vs. 99.1±18.9per minute, p value=0.005). Real-time AVF feedback can provide a better compression depth, rate, and effective compression ratio (6.16±1.88cm vs. 5.54±1.89cm, p value=0.02; 103.2±21.0/min vs. 96.7±25.8/min, p value=0.03; 62.6±28.0% vs. 51.0±33.2%, p value=0.004). Regardless of the effect of real-time feedback, the CC depth correlated to the rescuers' body weight. Rescuers who weighed below 71kg benefited from the Kinect module-based real-time AVF device in terms of improved CC quality. CONCLUSION: The Kinect-based AVF device can significantly improve CC quality in manikin training in rescuers with their body weight<71kg.

Usefulness of glycated hemoglobin A1c-based adjusted glycemic variables in diabetic patients presenting with acute ischemic stroke.

Acute hyperglycemia is a common condition among patients with diabetes who are admitted to the emergency department (ED) for acute ischemic stroke (AIS). Previous findings regarding the association between hyperglycemia at admission and adverse outcomes among patients with diabetes and AIS have been inconsistent. When investigating this association, it is necessary to consider premorbid blood glucose control. The objective of the current study was to assess whether HbA1c-based adjusted glycemic variables were associated with unfavorable outcomes among patients admitted to the hospital for AIS. We retrospectively analyzed data from 309 patients who were hospitalized for AIS at a single medical center in Taiwan between January 1, 2013, and October 31, 2015. We found that 1) HbA1c-based adjusted glycemic variables, including the glycemic gap and stress hyperglycemia ratio, were associated with both AIS severity and neurological status at discharge; additionally, 2) HbA1c-based adjusted glycemic variables showed superior discriminative power compared with acute hyperglycemia regarding the development of severe AIS. We conclude that both the glycemic gap and stress hyperglycemia ratio might be useful in assessing the disease severity and prognosis of patients presenting with AIS. Further prospective long-term follow-up studies should be performed to validate these findings.

Thyroid Storm in a Patient with Trauma - A Challenging Diagnosis for the Emergency Physician: Case Report and Literature Review.

BACKGROUND: Thyroid storm, an endocrine emergency, remains a diagnostic and therapeutic challenge. It is recognized to develop as a result of several factors, including infection, surgery, acute illness, and rarely, trauma. Recognition of thyroid storm in a trauma patient is difficult because the emergency physician usually focuses on managing more obvious injuries. OBJECTIVE OF THE REVIEW: We present a case of trauma-related thyroid storm and review the previous literature on posttraumatic thyroid storm to delineate risk factors of the disease. The case occurred in a 32-year-old man after a motorcycle accident. DISCUSSION: Careful investigation of patient history and risk factors of trauma-related thyroid storms and utilization of the scoring system may facilitate early diagnosis. Traumatically induced thyroid storm usually responds to medical treatment developed for hyperthyroidism. Surgical intervention may be needed for patients who failed medical treatment or those with direct thyroid gland injuries. The outcome is usually fair under appropriate management. CONCLUSION: We present a case of trauma-related thyroid storm to illustrate the diagnostic and therapeutic approach with a summary of the previous literature. Emergency physicians should be aware of the clinical presentation and risk factors of patients with trauma-related thyroid storm to reduce the rate of misdiagnosis and prevent catastrophic outcomes.

The physiological effects and quality of chest compressions during CPR at sea level and high altitude.

BACKGROUND: Rescuers that undergo acute ascent without acclimatization can experience acute mountain sickness. Although performing cardiopulmonary resuscitation (CPR) for a short period requires intensive effort at sea level, performing CPR at high altitude is even more exhausting and can endanger the rescuer. Therefore, we conducted a pilot study to compare the quality of resuscitation in health professionals at high altitude (3100 m) and that at sea level. METHODS: Thirty-eight participants were asked to performed continuous chest compression CPR (CCC-CPR) for 5 minutes at sea level and at high altitude. Cardiopulmonary resuscitation recording technology was used to objectively quantify the quality of the chest compressions (CCs), including the depth and rate thereof. RESULTS: At high altitude, rescuers showed a statistically significant decrease in blood oxygen saturation and an increase in systolic blood pressure, diastolic blood pressure, heart rate, and fatigue, as measured with the Borg score, after CCC-CPR compared with resting levels. The analysis of the time-dependent deterioration in the quality of CCC-CPR showed that the depth of CCs declined from the mean depth of the first 30 seconds after CCC-CPR to that at more than 120 seconds after CCC-CPR at both sea level and high altitude. The average number of effective CCs declined after CCC-CPR was performed for 1 minute at sea level and high altitude. CONCLUSIONS: The quality of CC rapidly declined at high altitude. At high altitude, the average number of effective CC decreases; and this decrease became significant after continuous CCs had been performed for 1 minute.

The associations among peptic ulcer disease, Helicobacter pylori infection, and abdominal aortic aneurysms: A nationwide population-based cohort study.

BACKGROUND: There are overlapping risk factors and underlying molecular mechanisms for both peptic ulcer disease (PUD) and abdominal aortic aneurysm (AAA). Despite improvements in the early diagnosis and treatment of AAA, ruptured AAAs continue to cause a substantial number of deaths. Helicobacter pylori are Gram-negative, microaerophilic bacteria that are now recognized as the main cause of PUD. H. pylori infection (HPI) is associated with an increased risk of certain cardiovascular diseases. HPIs can be treated with at least two different antibiotics to prevent bacteria from developing resistance to one particular antibiotic. METHODS: We conducted a population-based cohort study using the National Health Insurance Research Database to evaluate whether associations exist among PUD, HPI, and eradication therapy for HPI and AAA. The primary outcome of this study was the cumulative incidence of AAA among patients with or without PUD and HPI during the 14-year follow-up period. RESULTS: Our analysis included 7003 patients with PUD/HPI, 7003 patients with only PUD, and another 7003 age-, sex-, and comorbidity-matched controls from the database. We found that patients with PUD/HPI had a significantly increased risk of AAA compared to those with PUD alone and matched controls. The patients who had PUD/HPI had a significantly higher cumulative risk of developing AAA than those with PUD and the comparison group (2.67 % vs. 1.41 % vs. 0.73 %, respectively, p < 0.001). Among those patients with PUD/HPI, patients who had eradication therapy had a lower incidence of AAA than those without eradication therapy (2.46 % vs. 3.88 %, p = 0.012). CONCLUSIONS: We revealed an association among PUD, HPI, and AAA, even after adjusting for age, sex, comorbidities, and annual medical follow-up visits. Notably, we found that HPI eradication therapy reduced the incidence of AAA among patients with PUD.