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.

Association between gout and abdominal aortic aneurysm.

BACKGROUND: Previous studies have shown an association between hyperuricemia and microvascular diseases, but the association between uric acid and abdominal aortic aneurysm (AAA) remains unclear. The aim of this study was to determine the relationship between gout and AAA. METHODS: A population-based cohort study was conducted to validate the association between gout and AAA formation. The outcome in this study was the cumulative incidence of AAA in patients with or without gout during the 14-year follow-up period. RESULTS: Our analysis included 121,236 patients with gout and 121,236 propensity score-matched controls from the National Health Insurance Research Database in Taiwan. Compared to the controls, patients who had gout exhibited a significantly increased incidence of AAA development [adjusted hazard ratio (HR) = 2.465, p < 0.001]. We also found that patients who were treated with anti-gout medications had a significantly lower risk of being diagnosed with an AAA than patients who were not treated with anti-gout medications (adjusted HR = 0.489, p < 0.001). CONCLUSIONS: We have provided clinical evidence that gout is associated with the development of AAA.

Learning effectiveness of energy education in junior high schools: Implementation of action research and the predict-observe-explain model to STEM course.

This study designed an interdisciplinary energy education course that enables students to learn about wind power topics by following the predict-observe-explain (POE) model. Two rounds of action research involving eighth-grade students from a junior high school in Taiwan were conducted. The objective of this study was to determine the effectiveness of the inquiry-based model in an interdisciplinary energy education course and provide the observations as a reference for implementing fundamental education in energy-related domains. Pretest and posttest questionnaire responses were analyzed using the paired-sample t-test, and we discovered that (1) the POE inquiry-based model promoted independent and deep thinking and facilitated the acquisition of interdisciplinary energy knowledge; (2) the POE inquiry-based process boosted the students' self-confidence, gave them a sense of achievement, and prolonged their learning interest; and (3) the provision of simple steps and guidelines enabled the students to develop inquiry plans independently through practice and teamwork and without being limited by the scope of a given academic discipline. We also discovered that, through practice, the students could produce excellent detailed records within a limited time frame, even including students who were inattentive in class.

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.

miR-424/322 protects against abdominal aortic aneurysm formation by modulating the Smad2/3/runt-related transcription factor 2 axis.

Rupture of abdominal aortic aneurysms (AAAs) is one of the leading causes of sudden death in the elderly population. The osteogenic transcription factor runt-related gene (RUNX) encodes multifunctional mediators of intracellular signal transduction pathways in vascular remodeling and inflammation. We aimed to evaluate the roles of RUNX2 and its putative downstream target miR-424/322 in the modulation of several AAA progression-related key molecules, such as matrix metalloproteinases and vascular endothelial growth factor. In the GEO database, we found that male patients with AAAs had higher RUNX2 expression than did control patients. Several risk factors for aneurysm induced the overexpression of MMPs through RUNX2 transactivation, and this was dependent on Smad2/3 upregulation in human aortic smooth muscle cells. miR-424 was overexpressed through RUNX2 after angiotensin II (AngII) challenge. The administration of siRUNX2 and miR-424 mimics attenuated the activation of the Smad/RUNX2 axis and the overexpression of several AAA progression-related molecules in vitro. Compared to their littermates, miR-322 KO mice were susceptible to AngII-induced AAA, whereas the silencing of RUNX2 and the administration of exogenous miR-322 mimics ameliorated the AngII-induced AAA in ApoE KO mice. Overall, we established the roles of the Smad/RUNX2/miR-424/322 axis in AAA pathogenesis. We demonstrated the therapeutic potentials of miR-424/322 mimics and RUNX2 inhibitor for AAA progression.

The risk and timing of acute ischemic stroke after electrical cardioversion for atrial fibrillation in Taiwan: A nationwide population-based cohort study.

BACKGROUND: There is a positive association between electrical cardioversion (ECV) and acute ischemic stroke (AIS). Although 4 weeks of anticoagulation therapy after ECV in atrial fibrillation (AF) patients is generally suggested by current guidelines to reduce the risk of AIS, limited studies have been conducted in Asian populations to determine the risk and timing of AIS after ECV for AF in recent years. Therefore, we aim to use the National Health Insurance Research Database (NHIRD) in Taiwan to determine the risk and timing of AIS after ECV for AF. METHODS: The data analyzed in this nationwide population-based retrospective cohort study were obtained from the NHIRD in Taiwan. The outcome in this study was the cumulative incidence of AIS in patients with AF during 7-day and 30-day follow-up periods after the patients underwent ECV. RESULTS: Our analysis included 39,697 patients with AF, of whom 5723 received ECV and 5723 were propensity score-matched controls. Compared to the controls, patients who received ECV exhibited a significantly increased incidence of 7-day AIS development (adjusted hazard ratio [HR] = 1.524, p = 0.003). In contrast, the incidence of 30-day AIS development showed no significant increase (adjusted HR = 1.301, p = 0.426). CONCLUSIONS: AF patients who underwent ECV had a higher incidence of 7-day AIS development but not 30-day AIS development. Considering the timing of AIS development after ECV in AF patients, the optimal duration of antithrombotic therapy after ECV deserves further investigation.

An Adapted Hybrid Model for Hands-On Practice on Disaster and Military Medicine Education in Undergraduate Medical Students During the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in substantial impacts on all aspects of medical education. Modern health systems must prepare for a wide variety of catastrophic scenarios, including emerging infectious disease outbreaks and human and natural disasters. During the COVID-19 pandemic, while the use of traditional teaching methods has decreased, the use of online-based teaching methods has increased. COVID-19 itself and the accompanying infection control measures have restricted full-scale practice. Therefore, we developed an adapted hybrid model that retained adequate hands-on practice and educational equality, and we applied it with a group of undergraduate medical students participating in a mandatory disaster education course in a military medical school. Methods: The course covered the acquisition of skills used in emergency and trauma scenarios through designated interdisciplinary modules on disaster responses. Several asynchronous and synchronous online webinars were used in this one-credit mandatory disaster and military medicine education course. To allow opportunities for hands-on practice and ensure education equality, the students were divided into 15 groups, with 12 students in each group. The hands-on practice exercises were also recorded and disseminated to the students in the designated area for online learning. Results: A total of 164 3rd-year medical students participated in this mandatory disaster and military medicine course during the COVID-19 pandemic. The satisfaction survey response rate was 96.5%. The students were satisfied with the whole curriculum (3.8/5). Most of the free-text comments regarding the course represented a high level of appreciation. The students felt more confident in the knowledge and skills they gained in hands-on exercises than they did in the knowledge and skills they gained in online exercises. The students showed significant improvements in knowledge after the course. Conclusions: We demonstrated that this adapted hybrid arrangement provided an enhanced learning experience, but we also found that medical students were more confident in their knowledge and skills when they had real hands-on practice.

Pharmacological Activation Of Aldehyde Dehydrogenase 2 Protects Against Heatstroke-Induced Acute Lung Injury by Modulating Oxidative Stress and Endothelial Dysfunction.

Heatstroke (HS) can cause acute lung injury (ALI). Heat stress induces inflammation and apoptosis via reactive oxygen species (ROS) and endogenous reactive aldehydes. Endothelial dysfunction also plays a crucial role in HS-induced ALI. Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that detoxifies aldehydes such as 4-hydroxy-2-nonenal (4-HNE) protein adducts. A single point mutation in ALDH2 at E487K (ALDH2*2) intrinsically lowers the activity of ALDH2. Alda-1, an ALDH2 activator, attenuates the formation of 4-HNE protein adducts and ROS in several disease models. We hypothesized that ALDH2 can protect against heat stress-induced vascular inflammation and the accumulation of ROS and toxic aldehydes. Homozygous ALDH2*2 knock-in (KI) mice on a C57BL/6J background and C57BL/6J mice were used for the animal experiments. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro experiment. The mice were directly subjected to whole-body heating (WBH, 42°C) for 1 h at 80% relative humidity. Alda-1 (16 mg/kg) was administered intraperitoneally prior to WBH. The severity of ALI was assessed by analyzing the protein levels and cell counts in the bronchoalveolar lavage fluid, the wet/dry ratio and histology. ALDH2*2 KI mice were susceptible to HS-induced ALI in vivo. Silencing ALDH2 induced 4-HNE and ROS accumulation in HUVECs subjected to heat stress. Alda-1 attenuated the heat stress-induced activation of inflammatory pathways, senescence and apoptosis in HUVECs. The lung homogenates of mice pretreated with Alda-1 exhibited significantly elevated ALDH2 activity and decreased ROS accumulation after WBH. Alda-1 significantly decreased the WBH-induced accumulation of 4-HNE and p65 and p38 activation. Here, we demonstrated the crucial roles of ALDH2 in protecting against heat stress-induced ROS production and vascular inflammation and preserving the viability of ECs. The activation of ALDH2 by Alda-1 attenuates WBH-induced ALI in vivo.

The Association between Migraine and Abdominal Aortic Aneurysms: A Nationwide Population-Based Cohort Study.

Previous studies have indicated that patients with migraine have a higher prevalence of risk factors known to be associated with cardiovascular diseases. There are also shared epidemiology and molecular mechanisms between migraine and abdominal aortic aneurysm (AAA). We hypothesized that patients with migraine could have an increased risk of AAA. To test this hypothesis, we used the National Health Insurance Research Database (NHIRD) to evaluate whether associations exist between migraine and AAA. The data for this nationwide population-based retrospective cohort study were obtained from the NHIRD in Taiwan. The assessed study outcome was the cumulative incidence of AAA in patients with migraine during a 15-year follow-up period. Among the 1,936,512 patients from the NHIRD, 53,668 (2.77%) patients were identified as having been diagnosed with migraine. The patients with migraine had a significantly higher cumulative risk of 3.558 of developing an AAA 5 years after the index date compared with the patients without migraine. At the end of the 15-year follow-up period, a significantly higher incidence of AAA (0.98%) was observed in the patients with migraine than in those without migraine (0.24%). We revealed an association between the development of migraine and AAA.

Association between abdominal aortic aneurysms and alcohol-related diseases.

Heterogeneous associations exist between alcohol consumption and the initial presentation of cardiovascular diseases (CVDs). Studies regarding the association between abdominal aortic aneurysms (AAAs) and alcohol consumption are still limited and controversial. We hypothesize that patients with alcohol-related diseases are susceptible to AAA formation due to the presence of overlapping epidemiological factors and molecular mechanisms. We aimed to use a nationwide population-based retrospective cohort study to evaluate the association between alcohol-related diseases and AAA.The data were extracted from the National Health Insurance Research Database (NHIRD) in Taiwan. The study outcome assessed was the cumulative incidence of AAA in patients with alcohol-related diseases during a 14-year follow-up period.Our study included 22,878 patients who had alcohol-related diseases; these patients with alcohol-related diseases had a significantly higher cumulative risk of developing AAA 5 years after the index date than did the 91,512 patients without alcohol-related diseases. Patients with alcohol-related diseases also exhibited a significantly increased incidence of AAA compared with the incidence among patients without alcohol-related diseases, according to Cox regression analysis and Fine & Gray's competing risk model (adjusted hazard ratio = 2.379, 95% confidence interval = 1.653 -3.424, P < .001). In addition, male gender, older age, and chronic kidney disease were also associated with an increased risk of developing AAA. An interaction model showed that males with alcohol-related diseases had a 10.4-fold higher risk of AAA than did females without alcohol-related diseases.We observed an association between alcohol-related diseases and AAA even after adjusting for several comorbidities and medications in a nationwide population database.

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.

Pilot study of a longitudinal integrated disaster and military medicine education program for undergraduate medical students.

Disaster medicine education in medical curricula is scarce and frequently nonexistent. It is reasonable to initiate educational approaches for physicians in this field at the medical school level. An understanding of disaster medicine and the health care system during massive casualty incidents has been recommended as an integral part of the medical curriculum in the United States and Germany.The goal of the reformed curriculum was to develop a longitudinal integrated disaster and military medicine education program extending from the first year to the sixth year based on previously separated clinical and military medicine topics. Emergency medicine physicians, military emergency medical technicians, and Tactical Combat Casualty Care instructors formed an interprofessional faculty group and designed a learning curriculum.A total of 230 medical students participated in the revised disaster preparedness curriculum. Satisfaction survey response rates were high (201/230, 87.4%). Most of the free-text comments on the program were highly appreciative. The students considered the number of teaching hours for the whole program to be adequate. The students showed significant improvements in knowledge and judgment regarding disaster medicine after the program.We found that medical students were highly interested, were appreciative of, and actively participated in this longitudinal integrated disaster and military medicine education program, but gaps existed between the students' scores and the educators' expectations. The educators believed that the students needed more disaster preparedness knowledge and skills.

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 subsequent cardiovascular diseases.

BACKGROUND: Cardiovascular diseases (CVDs) and aortic aneurysms (AAs) share several clinical risk factors. However, the potential effects on future CVDs of surgical treatments involving the open surgical repair (OSR) of AAs are unknown. We hypothesize that the OSR of AAs is associated with subsequent CVDs. METHODS: The data for this nationwide population-based retrospective cohort study were obtained from the National Health Insurance Research Database in Taiwan. The outcome assessed in this study was the cumulative incidence of CVDs in patients with AAs during a 14-year follow-up period, which was further stratified according to those who underwent OSR, endovascular aneurysm repair (EVAR), and nonsurgical treatment (NST). RESULTS: Our analysis included 11,764 patients with AAs, of whom 2,524 received surgery and 2,524 were propensity score-matched controls. Compared to the controls, patients who received OSR exhibited a significantly decreased incidence of CVD development [adjusted hazard ratio (HR)=0.89,p=0.006]. Furthermore, compared to patients who received NST, patients who received OSR had a significantly lower incidence of subsequent acute myocardial infarction (adjusted HR=0.793, p=0.037). CONCLUSIONS: Compared to NST, OSR of AAs could be associated with a lower incidence of subsequent CVDs.

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.

An elevated glycemic gap predicts adverse outcomes in diabetic patients with necrotizing fasciitis.

BACKGROUND: Diabetes is the most common comorbidity of necrotizing fasciitis (NF), but the effect of stress-induced hyperglycemia (SIH) on diabetic patients with NF has never been investigated. The aim of this study was to assess whether SIH, as determined by the glycemic gap between admission glucose levels and A1C-derived average glucose levels, predicts adverse outcomes in diabetic patients hospitalized with NF. METHODS: We retrospectively reviewed the glycemic gap and clinical outcomes in 252 diabetic patients hospitalized due to NF from 2011 to 2018 in a single medical center in Taiwan. A receiver operating characteristic (ROC) curve was used to analyze the optimal cutoff values for predicting adverse outcomes. Univariate and multivariate logistic regression analyses were employed to identify significant predictors of adverse outcomes. RESULTS: In total, 194 diabetic NF patients were enrolled. Compared with patients without adverse outcomes, patients with adverse outcomes had significantly higher glycemic gaps, Acute Physiology and Chronic Health Evaluation (APACHE) II scores and C-reactive protein (CRP) levels; lower albumin and hemoglobin levels; greater incidence of limb loss; and longer hospital and intensive care unit stays. The glycemic gap positively correlates with the laboratory risk indicator for NF scores, APACHE II scores and CRP levels. A glycemic gap of 146 mg/dL was the optimal cutoff value for predicting adverse outcomes using the ROC curve. Compared with patients with glycemic gaps ≤146 mg/dL, those with glycemic gaps >146 mg/dL had higher APACHE II scores and incidence rates of adverse outcomes, especially bacteremia and acute kidney injury. Multivariate analysis revealed that a glycemic gap >146 mg/dL and APACHE II score >15 were independent predictors of adverse outcomes, while the presence of hyperglycemia at admission was not. CONCLUSIONS: An elevated glycemic gap was significantly independently associated with adverse outcomes in diabetic NF patients. Further prospective studies are warranted to validate the role of the glycemic gap in NF patients with diabetes.

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.