Factors Associated With Unhealthy Weight Control Behaviors Among a Representative Sample of U.S. High School Students.

Adolescents often practice unhealthy behaviors to lose weight or keep from gaining weight. Centers for Disease Control and Prevention has conducted biennial Youth Risk Behavior Survey (YRBS) of various health risk behaviors since 1991 using U.S. representative samples of high school students and is therefore best for us to identify risk/preventive factors associated with unhealthy weight control behaviors (UWCB). We quantitatively assessed the association between various health risk behaviors with UWCB by gender using YRBS data. Due to the absence of UWCB items since 2015, we analyzed the latest (2013) data using binary multiple logistic regression. Among the 13,583 participants, 22.7% of girls and 10.1% of boys engaged in UWCB. Among girls and boys separately, the common significant factors included suicidal behaviors, alcohol drinking, misused prescription drug, feeling depressed, skipping breakfast, and attending physical education class. School nurses are suggested to have knowledge about the aforementioned risk factors and provide assessment, consultation, and education to help reduce UWCB.

Aortic Thrombus in a Nonaneurysmal Ascending Aorta.

BACKGROUND: Ascending aortic thrombus (AAT) in a nonaneurysmal aorta is an extremely rare event and has potentially catastrophic complications, with a life-threatening risk of myocardial infarction and cerebral embolization. This systematic review aims to elucidate the clinical manifestations and to compare the outcomes of anticoagulation therapy versus open aortic surgery for AAT. METHODS: The MEDLINE/PubMed databases were extensively searched between 1995 and 2019. All relevant publications on AAT in adults were reviewed, and individual patient data were pooled in this meta-analysis. The primary outcome was AAT resolution. The adverse outcome variables were recurrent arterial embolic events, complications related to open aortic surgery, and mortality during the study period. Chi-squared test and logistic regression analysis were used to compare groups and identify any predictors of mortality. RESULTS: Overall, 107 patients from 101 articles were included, of whom 29 patients who received anticoagulation therapy and 59 who underwent open aortic surgery were included in the outcome analysis. Among 29 patients treated with initial anticoagulation therapy, the persistence of AAT was observed in 11 patients (38%) and recurrent arterial embolization was developed in 6 patients (21%). All 11 patients in the anticoagulation group underwent secondary aortic surgery for the persistence of AAT with uneventful postoperative course. Compared with patients treated with primary aortic surgery, patients treated with initial anticoagulation therapy had higher risk of recurrent embolization (P = 0.002). No significant difference existed in the mortality rates between the groups (P = 0.106). Hemodynamic instability was an independent predictor of mortality (P = 0.008). CONCLUSIONS: Anticoagulation therapy and open aortic surgery for AAT show similar results; however, open aortic surgery reliably removes AAT and reduces the risk of recurrent embolization compared with anticoagulation therapy. Furthermore, the preoperative hemodynamic status significantly influences the clinical outcome and is a strong predictor of prognosis.

Examining the Effectiveness of 3D Virtual Reality Training on Problem-solving, Self-efficacy, and Teamwork Among Inexperienced Volunteers Helping With Drug Use Prevention: Randomized Controlled Trial.

BACKGROUND: Illegal drug usage among adolescents is a critical health problem. The Taiwanese government provides an accompanying volunteer program to prevent students who experiment with drugs from reusing them. An appropriate training program can improve volunteers' abilities to assist students using drugs. Problem-solving, self-efficacy, and teamwork are critical abilities for inexperienced volunteers who help with drug use prevention. By interacting with the animation or 3D virtual reality (VR) in the virtual scene, learners can immerse themselves in the virtual environment to learn, and 3D VR can increase learning opportunities and reduce the cost of human and material resources. OBJECTIVE: The aim of this study was to examine the effectiveness of spherical video-based virtual reality (SVVR) training in improving problem-solving, self-efficacy, and teamwork among volunteers who helped prevent adolescents from using illegal drugs. METHODS: This study used a randomized controlled design with a total of 68 participants in the experimental (n=35) and control (n=33) groups. The participants in the experimental group received the SVVR training program and their counterparts in the control group did not receive any training. RESULTS: Generalized estimating equation analyses indicated that the experimental group showed significant posttraining improvements in problem-solving and self-efficacy but not teamwork when compared with the control group. CONCLUSIONS: The results of this study revealed that SVVR could improve participants' problem-solving skills and self-efficacy for assisting students in not using illegal drugs. However, future studies are suggested to develop effective SVVR to assist inexperienced volunteers in enhancing their teamwork abilities. We believed that introducing the training program to more sites can enhance volunteer training so that volunteers can have a better companionship effect when helping students quit drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05072431; https://clinicaltrials.gov/ct2/show/NCT05072431.

Intravenous administration of iPS-MSCSPIONs mobilized into CKD parenchyma and effectively preserved residual renal function in CKD rat.

This study traced intravenously administered induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSC) and assessed the impact of iPSC-MSC on preserving renal function in SD rat after 5/6 nephrectomy. The results of in vitro study showed that FeraTrack™Direct contrast particles (ie intracellular magnetic labelling) in the iPSC-MSC (ie iPS-MSCSPIONs ) were clearly identified by Prussian blue stain. Adult-male SD rats (n = 40) were categorized into group 1 (SC), group 2 [SC + iPS-MSCSPIONs (1.0 × 106 cells)/intravenous administration post-day-14 CKD procedure], group 3 (CKD), group 4 [CKD + iPS-MSCSPIONs (0.5 × 106 cells)] and group 5 [CKD + iPS-MSCSPIONs (1.0 × 106 cells)]. By day-15 after CKD induction, abdominal MRI demonstrated that iPS-MSCSPIONs were only in the CKD parenchyma of groups 4 and 5. By day 60, the creatinine level/ratio of urine protein to urine creatinine/kidney injury score (by haematoxylin and eosin stain)/fibrotic area (Masson's trichrome stain)/IF microscopic finding of kidney injury molecule-1 expression was lowest in groups 1 and 2, highest in group 3, and significantly higher in group 4 than in group 5, whereas IF microscopic findings of podocyte components (ZO-1/synaptopodin) and protein levels of anti-apoptosis ((Bad/Bcl-xL/Bcl-2) exhibited an opposite pattern to creatinine level among the five groups (all P < .0001). The protein expressions of cell-proliferation signals (PI3K/p-Akt/m-TOR, p-ERK1/2, FOXO1/GSK3ß/p90RSK), apoptotic/DNA-damage (Bax/caspases8-10/cytosolic-mitochondria) and inflammatory (TNF-α/TNFR1/TRAF2/NF-κB) biomarkers displayed an identical pattern to creatinine level among the five groups (all P < .0001). The iPS-MSCSPIONs that were identified only in CKD parenchyma effectively protected the kidney against CKD injury.

MicroRNA-214 modulates the senescence of vascular smooth muscle cells in carotid artery stenosis.

BACKGROUND: MicroRNAs control gene expression by post-transcriptional inhibition. Dysregulation of the expressions of miR-199a/214 cluster has been linked to cardiovascular diseases. This study aimed at identifying potential microRNAs related to vascular senescence. METHODS: Seven candidate microRNAs (miR-19a, -20a, -26b, -106b, - 126, - 214, and - 374) related to cell proliferation were tested for their expressions under CoCl2-induced hypoxia in vascular smooth muscle cells (VSMCs). After identification of miR-214 as the candidate microRNA, telomere integrity impairment and cell cycle arrest were examined in VSMCs by using miR-214 mimic, AntagomiR, and negative controls. To investigate the clinical significance of miR-214 in vascular diseases, its plasma level from patients with carotid artery stenosis (CAS) was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: CoCl2 treatment for 48 h suppressed cell proliferation and angiogenesis as well as enhanced cell senescence in VSMCs. Besides, miR-214 level was elevated in both intracellular and exosome samples of VSMCs after CoCl2 treatment. Manipulating miR-214 in VSMCs demonstrated that miR-214 not only inhibited angiogenic and proliferative capacities but also promoted senescence through the suppression of quaking. Additionally, circulating miR-214 level was upregulated in CAS patients with high low-density lipoprotein cholesterol (LDL-C) value. CONCLUSION: Our findings suggested that miR-214 plays a role in the modulation of VSMC angiogenesis, proliferation, and senescence with its plasma level being increased in CAS patients with elevated LDL-C value, implying that it may be a vascular senescence marker and a potential therapeutic target for vascular diseases.

Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34+ Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia.

This study tested whether circulatory endothelial progenitor cells (EPCs) derived from peripheral arterial occlusive disease (PAOD) patients after receiving combined autologous CD34+ cell and hyperbaric oxygen (HBO) therapy (defined as rejuvenated EPCs) would salvage nude mouse limbs against critical limb ischemia (CLI). Adult-male nude mice (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (CLI), group 3 (CLI-EPCs (6 × 105) derived from PAOD patient's circulatory blood prior to CD34+ cell and HBO treatment (EPCPr-T) by intramuscular injection at 3 h after CLI induction) and group 4 (CLI-EPCs (6 × 105) derived from PAOD patient's circulatory blood after CD34+ cell and HBO treatment (EPCAf-T) by the identical injection method). By 2, 7 and 14 days after the CLI procedure, the ischemic to normal blood flow (INBF) ratio was highest in group 1, lowest in group 2 and significantly lower in group 4 than in group 3 (p < 0.0001). The protein levels of endothelial functional integrity (CD31/von Willebrand factor (vWF)/endothelial nitric-oxide synthase (eNOS)) expressed a similar pattern to that of INBF. In contrast, apoptotic/mitochondrial-damaged (mitochondrial-Bax/caspase-3/PARP/cytosolic-cytochrome-C) biomarkers and fibrosis (Smad3/TGF-ß) exhibited an opposite pattern, whereas the protein expressions of anti-fibrosis (Smad1/5 and BMP-2) and mitochondrial integrity (mitochondrial-cytochrome-C) showed an identical pattern of INBF (all p < 0.0001). The protein expressions of angiogenesis biomarkers (VEGF/SDF-1α/HIF-1α) were progressively increased from groups 1 to 3 (all p < 0.0010). The number of small vessels and endothelial cell surface markers (CD31+/vWF+) in the CLI area displayed an identical pattern of INBF (all p < 0.0001). CLI automatic amputation was higher in group 2 than in other groups (all p < 0.001). In conclusion, EPCs from HBO-C34+ cell therapy significantly restored the blood flow and salvaged the CLI in nude mice.

A Cross-Sectional Examination of the Factors Related to Emergency Nurses' Motivation to Protect Themselves Against an Ebola Infection.

INTRODUCTION: The 2014-2016 West African Ebola outbreak impacted the United States. Owing to the sporadic occurrence of the Ebola infection, there is insufficient research regarding how US emergency nurses provide care to patients potentially infected with the Ebola virus and the nurses' motivation to protect themselves when providing care to these patients. This study aimed to investigate the predictors of emergency nurses' protection motivation. METHODS: A cross-sectional design was employed. A survey developed based on a modified Protection Motivation Theory was administered to randomly selected members of the Emergency Nurses Association. Descriptive statistics, nonparametric Kruskal-Wallis H test (as well as post hoc Dunn-Bonferroni test), Spearman rho correlation, and stepwise multiple linear regression were conducted for data analysis. RESULTS: Protection motivation was found in 2 components: proactive and passive protection motivation. Regression analysis indicated that response efficacy (ß = 0.27, P < 0.001) and self-efficacy (ß = 0.17, P < 0.01) significantly predict emergency nurses' proactive protection motivation, whereas perceived vulnerability (ß = 0.26, P < 0.001), response cost (ß = 0.19, P = 0.001), and knowledge (ß = -0.15, P < 0.01) significantly predict emergency nurses' passive protection motivation. DISCUSSION: The results indicate the need for interventions to improve emergency nurses' response efficacy, self-efficacy, and knowledge, while simultaneously reducing the nurses' perceived vulnerability and response cost. Such interventions would be expected to proactively motivate nurses to protect themselves when providing care to patients who exhibit the signs and symptoms of an Ebola infection and reduce their passive protection motivation.

Left Ventricle Decompression Strategies in Pediatric Peripheral Extracorporeal Membrane Oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is widely used in patients with potentially reversible acute cardiac and/or pulmonary failure who are unresponsive to conventional treatment. Patients with profound left ventricular (LV) dysfunction under venous-arterial (V-A) ECMO may experience LV distention, pulmonary edema, and thrombus formation. It is critical to unload the left ventricle to prevent such complications. The aim of this study was to identify the risks, timing and methods of LV decompression in pediatric peripheral ECMO. METHODS: Between August 2006 and November 2017, 51 patients received peripheral ECMO support in our pediatric intensive care unit. All of them were less than 18 years of age and non-cardiotomy surgery-related. We retrospectively reviewed the patients' clinical presentations, decompression methods and outcomes. RESULTS: The overall success rate of ECMO removal was 76.5% (39/51), and the survival rate after discharge was 62.7% (32/51). The myocarditis group had the most favorable outcomes among the ECMO patients (100% survival). LV decompression was needed in 12 patients who had profound LV dysfunction under V-A ECMO. Five patients received medical treatment successfully, and the other 7 patients underwent intra-aortic balloon pump (IABP) procedures. In the IABP group, 1 patient still needed further pigtail-decompression. All of our decompression patients survived with good neurological outcomes (Glasgow Outcome Scale 5). CONCLUSIONS: The patients with profound LV dysfunction under peripheral VA ECMO were at risk of thromboembolic events and LV decompress was needed. If medical decompression fails, IABP is a feasible approach for LV decompression in pediatric peripheral ECMO.

The Five-Year Clinical and Angiographic Follow-Up Outcomes of Intracoronary Transfusion of Circulation-Derived CD34+ Cells for Patients With End-Stage Diffuse Coronary Artery Disease Unsuitable for Coronary Intervention-Phase I Clinical Trial.

OBJECTIVES: This study investigated the clinical and angiographic long-term outcomes of intracoronary transfusion of circulation-derived CD34+ cells for patients with end-stage diffuse coronary artery disease unsuitable for coronary intervention. DESIGN AND SETTING: A single-center prospective randomized double-blinded phase I clinical trial. Thirty-eight patients undergoing CD34+ cell therapy were allocated into groups 1 (1.0 × 10 cells/each vessel; n = 18) and 2 (3.0 × 10 cells/each vessel; n = 20). PATIENTS: Those with end-stage diffuse coronary artery disease were unsuitable for percutaneous and surgical coronary revascularization. INTERVENTIONS: Intracoronary delivery of circulation-derived CD34+ cells. MEASUREMENTS AND MAIN RESULTS: We prospectively evaluated long-term clinical and echocardiographic/angiographic outcomes between survivors and nonsurvivors. By the end of 5-year follow-up, the survival rate and major adverse cardio/cerebrovascular event were 78.9% (30/38) and 36.8% (14/38), respectively. During follow-up period, 31.6% patients (12/38) received coronary stenting for reason of sufficient target vessel size grown-up after the treatment. Endothelial function was significantly reduced in the nonsurvivors than the survivors (p = 0.039). Wimasis image analysis of angiographic findings showed that the angiogenesis was significantly and progressively increased from baseline to 1 and 5 years (all p < 0.001). The 3D echocardiography showed left ventricular ejection fraction increased from baseline to 1 year and then remained stable up to 5 years, whereas left ventricular chamber diameter exhibited an opposite pattern to left ventricular ejection fraction among the survivors. The clinical scores for angina and heart failure were significantly progressively reduced from baseline to 1 and 5 years (all p < 0.001). CONCLUSIONS: CD34+ cell therapy for end-stage diffuse coronary artery disease patients might contribute to persistently long-term effects on improvement of left ventricular function, angina/heart failure, and amelioration of left ventricular remodeling.

Daily melatonin protects the endothelial lineage and functional integrity against the aging process, oxidative stress, and toxic environment and restores blood flow in critical limb ischemia area in mice.

We tested the hypothesis that daily melatonin treatment protects endothelial lineage and functional integrity against the aging process, oxidative stress/endothelial denudation (ED), and toxic environment and restored blood flow in murine critical limb ischemia (CLI). In vitro study using HUVECs, in vivo models (ie, CLI through left femoral artery ligation and ED through carotid artery wire injury), and model of lipopolysaccharide-induced aortic injury in young (3 months old) and aged (8 months old) mice were used to elucidate effects of melatonin treatment on vascular endothelial integrity. In vitro study showed that menadione-induced oxidative stress (NOX-1/NOX-2), inflammation (TNF-α/NF-kB), apoptosis (cleaved caspase-3/PARP), and mitochondrial damage (cytosolic cytochrome c) in HUVECs were suppressed by melatonin but reversed by SIRT3-siRNA (all P < .001). In vivo, reduced numbers of circulating endothelial progenitor cells (EPCs) (C-kit/CD31+/Sca-1/KDR+/CXCR4/CD34+), and angiogenesis (Matrigel assay of bone marrow-derived EPC and ex vivo aortic ring cultures) in older (compared with younger) mice were significantly reversed through daily melatonin administration (20 mg/kg/d, ip) (all P < .001). Aortic vasorelaxation and nitric oxide release were impaired in older mice and reversed in age-match mice receiving melatonin (all P < .01). ED-induced intimal/medial hyperplasia, reduced blood flow to ischemic limb, and angiogenesis (reduced CD31+/vWF+ cells/small vessel number) were improved after daily melatonin treatment (all P < .0001). Lipopolysaccharide-induced aortic endothelial cell detachment, which was more severe in aged mice, was also alleviated after daily melatonin treatment (P < .0001). Daily melatonin treatment protected both structural and functional integrity of vascular endothelium against aging-, oxidative stress-, lipopolysaccharide-, and ischemia-induced damage probably through upregulating the SIRT signaling pathway.

Shock Wave Therapy Enhances Mitochondrial Delivery into Target Cells and Protects against Acute Respiratory Distress Syndrome.

This study tested the hypothesis that shock wave therapy (SW) enhances mitochondrial uptake into the lung epithelial and parenchymal cells to attenuate lung injury from acute respiratory distress syndrome (ARDS). ARDS was induced in rats through continuous inhalation of 100% oxygen for 48 h, while SW entailed application 0.15 mJ/mm2 for 200 impulses at 6 Hz per left/right lung field. In vitro and ex vivo studies showed that SW enhances mitochondrial uptake into lung epithelial and parenchyma cells (all p < 0.001). Flow cytometry demonstrated that albumin levels and numbers of inflammatory cells (Ly6G+/CD14+/CD68+/CD11b/c+) in bronchoalveolar lavage fluid were the highest in untreated ARDS, were progressively reduced across SW, Mito, and SW + Mito (all p < 0.0001), and were the lowest in sham controls. The same profile was also seen for fibrosis/collagen deposition, levels of biomarkers of oxidative stress (NOX-1/NOX-2/oxidized protein), inflammation (MMP-9/TNF-α/NF-κB/IL-1ß/ICAM-1), apoptosis (cleaved caspase 3/PARP), fibrosis (Smad3/TGF-ß), mitochondrial damage (cytosolic cytochrome c) (all p < 0.0001), and DNA damage (γ-H2AX+), and numbers of parenchymal inflammatory cells (CD11+/CD14+/CD40L+/F4/80+) (p < 0.0001). These results suggest that SW-assisted Mito therapy effectively protects the lung parenchyma from ARDS-induced injury.

Combined Therapy with SS31 and Mitochondria Mitigates Myocardial Ischemia-Reperfusion Injury in Rats.

Myocardial ischemia-reperfusion (IR) injury contributes to adverse cardiac outcomes after myocardial ischemia, cardiac surgery, or circulatory arrest. In this study, we evaluated the ability of combined SS31-mitochondria (Mito) therapy to protect heart cells from myocardial IR injury. Adult male SD rats (n = 8/each group) were randomized: group 1 (sham-operated control), group 2 (IR, 30-min ischemia/72 h reperfusion), group 3 (IR-SS31 (2 mg intra-peritoneal injection at 30 min/24 h/48 h after IR)), group 4 (IR-mitochondria (2 mg/derived from donor liver/intra-venous administration/30 min after IR procedure)), and group 5 (IR-SS31-mitochondria). In H9C2 cells, SS31 suppressed menadione-induced oxidative-stress markers (NOX-1, NOX-2, oxidized protein) while it increased SIRT1/SIRT3 expression and ATP levels. In adult male rats 72 h after IR, left ventricular ejection fraction (LVEF) was highest in sham-operated control animals and lowest in the IR group. LVEF was also higher in IR rats treated with SS31-Mito than untreated IR rats or those treated with Mito or SS31 alone. Areas of fibrosis/collagen-deposition showed the opposite pattern. Likewise, levels of oxidative-stress markers (NOX-1, NOX-2, oxidized protein), inflammatory markers (MMP-9, CD11, IL-1ß, TNF-α), apoptotic markers (mitochondrial-Bax, cleaved-caspase-3, PARP), fibrosis markers (p-Smad3, TGF-ß), DNA-damage (γ-H2AX), sarcomere-length, and pressure/volume overload markers (BNP, ß-MHC) all showed a pattern opposite that of LVEF. Conversely, anti-apoptotic (BMP-2, Smad1/5) and energy integrity (PGC-1α/mitochondrial cytochrome-C) markers exhibited a pattern identical to that of LVEF. This study demonstrates that the combined SS31-Mito therapy is superior to either therapy alone for protecting myocardium from IR injury and indicates that the responsible mechanisms involved increased SIRT1/SIRT3 expression, which suppresses inflammation and oxidative stress and protects mitochondrial integrity.

GORE-TEX VASCULAR GRAFT FOR MACULAR BUCKLING IN HIGH MYOPIA EYES.

PURPOSE: To evaluate a new application of an expanded polytetrafluoroethylene (Gore-Tex) vascular graft for use in macular buckling surgery for treatment of highly myopic eyes. METHODS: The Gore-Tex vascular graft was used as a macular buckling material in eight consecutive cases of myopic macular diseases which included fovea detachment, foveoschisis, or macular hole retinal detachment. RESULTS: Retinal reattachment was achieved in all cases except one which had partial resolution (88%). The postoperative best-corrected visual acuity ranged from 20/2000 to 20/100 depending on the degree preexisting macular degeneration, and significant better than the preoperative best-corrected visual acuity (P = 0.048, paired t-test). During the follow-up period, which ranged from 8 months to 3 years, no eye developed buckle-related complications such as infection or dislocation. CONCLUSION: The initial pilot results from this series using a Gore-Tex graft for macular buckling is promising. Throughout the follow-up period, the Gore-Tex was well tolerated in the highly myopic eyes. Large scale and long-term follow-up is warranted.

Predicting Racial and Ethnic Disparities in Advance Care Planning Using the Integrated Behavioral Model.

Purpose To explain and predict racial or ethnic disparities in advance care planning (ACP) behaviors among American adults by using the Integrated Behavioral Model (IBM) and the Precaution Adoption Process Model. Methods A randomized, observational, nonexperimental, cross-sectional study design was used to survey American adults between 40 and 80 years of age ( n = 386). Results The majority of respondents (75%) had not completed ACP. Significant differences were found by race or ethnicity: 33% of Whites had completed ACP versus Hispanics (18%) and Blacks (8%). Whites had statistically significantly higher levels of most IBM constructs compared with Blacks and Hispanics. The IBM predicted 28% of the variance in behavioral intention. After controlling for sociodemographic variables, direct attitudes, indirect attitudes, and indirect perceived norms were significant predictors of behavioral intention. Conclusion The IBM and the Precaution Adoption Process Model are useful frameworks for interventions designed to increase ACP among racial or ethnic minorities in the United States.

Early Administration of Carvedilol Protected against Doxorubicin-Induced Cardiomyopathy.

This study tested for the benefits of early administration of carvedilol as protection against doxorubicin (DOX)-induced cardiomyopathy. Thirty male, adult B6 mice were categorized into group 1 (untreated control), group 2 [DOX treatment (15 mg/every other day for 2 weeks, i.p.], and group 3 [carvedilol (15 mg/kg/d, from day 7 after DOX treatment for 28 days)], and euthanized by day 35 after DOX treatment. By day 35, the left ventricular ejection fraction (LVEF) was significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1, whereas the left ventricular (LV) end-diastolic and LV end-systolic dimensions showed an opposite pattern to the LVEF among the three groups. The protein expressions of fibrotic (Smad3, TGF-ß), apoptotic (BAX, cleaved caspase 3, PARP), DNA damage (γ-H2AX), oxidative stress (oxidized protein), mitochondrial damage (cytosolic cytochrome-C), heart failure (brain natriuretic peptide), and hypertrophic (ß-MHC) biomarkers of the LV myocardium showed an opposite pattern to the LVEF among the three groups. The protein expressions of antifibrotic (BMP-2, Smad1/5), α-MHC, and phosphorylated-Akt showed an identical pattern to the LVEF among the three groups. The microscopic findings of fibrotic and collagen-deposition areas and the numbers of γ-H2AX(+) and 53BP1(+) cells in the LV myocardium exhibited an opposite pattern, whereas the numbers of endothelial cell (CD31(+), vWF(+)) markers showed an identical pattern to the LVEF among the three groups. Cardiac stem cell markers (C-kit(+) and Sca-1(+) cells) were significantly and progressively increased from group 1 to group 3. Additionally, the in vitro study showed carvedilol treatment significantly inhibited DOX-induced cardiomyoblast DNA (CD90/XRCC1(+), CD90/53BP1(+), and r-H2AX(+) cells) damage. Early carvedilol therapy protected against DOX-induced DNA damage and cardiomyopathy.

Administered circulating microparticles derived from lung cancer patients markedly improved angiogenesis, blood flow and ischemic recovery in rat critical limb ischemia.

BACKGROUND: We hypothesized that lung cancer patient's circulating microparticles (Lc-MPs) could promote angiogenesis, blood flow in ischemic zone and ischemic recovery in rat critical limb ischemia (CLI). METHODS: To investigate the impact of MP therapy on reversing the setting of CLI, adult-male Sprague-Dawley rats (n=50) equally randomized into sham control (SC) (group 1), SC-Lc-MPs (1.0 x 10(7) particles) (group 2), CLI (group 3), CLI-Hs-MPs (MPs from healthy-subject) (group 4), and CLI-Lc-MPs (group 5) were sacrificed by post-CLI day-14. RESULTS: In vitro study showed that Lc-MPs enhanced VEGFR2 expression, angiogenesis, nitric-oxide production, and endothelial cell proliferation (all p<0.005). By days 7 and 14, Laser Doppler showed significantly higher ischemic/normal blood-flow ratio in groups 1 and 2 compared with group 3, and was significantly higher in group 4 and further elevated in group 5 (p<0.0001). Numbers of small vessels and endothelial markers (CD31(+) and vWF(+) cells) and protein expressions (eNOS, CD31) exhibited a pattern identical to Lasre Doppler among the five groups (all p<0.001). Pro-angiogenic factors (VEGF, CXCR4, SDF-1α, HGF) at cellular and protein levels showed a significant step-wise increase from groups 1 and 2 to groups 3, 4, and 5 (all p<0.001). Protein expressions of fibrotic (Smad3, TGF-ß) and apoptotic (mitochondrial Bax, cleaved caspase 3, and PARP) biomarkers displayed an opposite pattern compared to that of Laser Doppler, whereas the protein expressions of anti-fibrotic (Smad1/5, BMP-2) and anti-apoptotic (Bcl-2) biomarkers showed an identical pattern compared with that of Laser Doppler among groups 1 to 3, and 5 (all p<0.001). CONCLUSION: Administration of Lc-MPs augmented angiogenesis and restored blood flow in a rat of CLI.

Combined melatonin and exendin-4 therapy preserves renal ultrastructural integrity after ischemia-reperfusion injury in the male rat.

We tested whether combined melatonin (Mel) and exendin-4 (Ex4) treatment can better preserve glomerular structural integrity after ischemia-reperfusion (IR) injury compared with either alone. Adult male Sprague Dawley rats (n = 50) were equally divided into sham control (SC), IR, IR-Ex4 (10 µg/kg subcutaneously 30 min after reperfusion and daily for 5 days), IR-Mel (20 mg/kg intraperitoneally at 30 min postreperfusion and 50 mg/kg at 6 and 18 hr), and IR-Ex4-Mel were euthanized at day 14. Serum creatinine level and urine protein-to-creatinine ratio at days 3 and 14 were highest in IR group and lowest in SC, significantly higher in IR-Ex4 and IR-Mel groups than in IR-Ex4-Mel group (all P < 0.001) without significant difference between IR-Ex4 and IR-Mel groups. Changes in podocyte injury score (PIS) and kidney injury score were highest in IR group and lowest in SC, significantly higher in IR-Ex4 and IR-Mel groups than in IR-Ex4-Mel, and significantly higher in IR-Mel group than in IR-Ex4 group (all P < 0.001). Immunohistochemical microscopic findings of the expressions of FSP-1 and WT-1 (two glomerular damage indicators) and KIM-1 and snail (two renal tubular-damaged indicators) showed an identical pattern, whereas the expressions of ZO-1, p-cadherin, podocin, dystroglycan, fibronectin, and synaptopodin (six indices of glomerular integrity) demonstrated an opposite pattern compared to that of PIS among five groups (all P < 0.001). Protein expressions of inflammatory (TNF-α/NF-κB/MMP-9) and oxidative stress (NOX-1, NOX-2, oxidized protein) biomarkers exhibited an identical pattern to that of PIS among five groups (all P < 0.001). Combined melatonin-exednin-4 therapy further protected glomerulus from IR injury.

African American legislators' perceptions of firearm violence prevention legislation.

Firearm mortality is the leading cause of death for young African American males, however, few studies have focused on racial/ethnic minority populations and firearm violence. The National Black Caucus of State Legislators advocates for legislation that promotes the health of African Americans. Thus, the purpose of this study was to collect baseline data on African American legislators' perceptions regarding firearm violence in the African American community. A cross-sectional study of African American legislators (n = 612) was conducted to investigate the research questions. Of the 612 questionnaires mailed, 12 were not deliverable, and 170 were returned (28%). Utilizing a three wave mailing process, African American legislators were invited to participate in the study. The majority (88%) of respondents perceived firearm violence to be very serious among African Americans. Few (10%) legislators perceived that addressing legislative issues would be an effective strategy in reducing firearm violence among African Americans. The majority (72%) of legislators perceived the most effective strategy to reducing firearm violence in the African American community should focus on addressing societal issues (e.g. crime and poverty). After adjusting for the number of perceived barriers, the number of perceived benefits was a significant predictor of legislators' perceived effectiveness of firearm violence prevention legislation for 8 of the 24 potential firearm violence prevention legislative bills.

Inhibition of dipeptidyl peptidase-IV enzyme activity protects against myocardial ischemia-reperfusion injury in rats.

BACKGROUND: We investigated whether attenuating dipeptidyl peptidase-IV (DPP4) enzyme activity protected rat heart from ischemia-reperfusion (IR) injury (40-min left anterior descending coronary artery ligation followed by 72 h reperfusion). METHODS AND RESULTS: Adult male Fischer 344 rats (n = 24) were equally divided into sham-control (WT-SC), WT-IR, and WT-IR-Sita (oral sitagliptin 400 mg/kg/day for 3 days) groups, whereas adult male DPP4-deficiency (DPP4(D)) rats (n = 16) were equally divided into DPP4(D)-SC and DPP4(D)-IR groups. Animals were sacrificed at 72 h after reperfusion with collection of heart specimens. Infarct area (H&E), collagen deposition (Sirius-red stain), fibrotic area (Masson's trichrome), and fluorescent-ROS intensity (H2DCFDA-labeling myocardium) of left ventricle were significantly higher in WT-IR than those in other groups, significantly higher in WT-IR-Sita and DPP4(D)-IR groups than in WT-SC and DPP4(D)-SC groups (all p < 0.001), but there was no difference between the latter two groups. Protein expressions of oxidative stress (oxidized protein), reactive oxygen species (NOX-1, NOX-2), inflammation (TNF-α, NF-κB, MMP-9, VCAM-1), apoptosis (mitochondrial Bax, cleaved caspase-3 and PARP), myocardial damage markers (cytosolic cytochrome-C, γ-H2AX), and number of inflammatory cells (CD14+, CD68+, CD40+ cells) showed a pattern identical to that of histological changes among all groups (all p < 0.005), whereas markers of anti-apoptosis (Bcl-2) and mitochondrial integrity (mitochondrial cytochrome-C) as well as left ventricular ejection fraction showed an opposite pattern (all p < 0.001). Protein expressions of anti-oxidants (HO-1, NQO-1), angiogenesis factors (SDF-1α, CXCR4), and glycogen-like-peptide-1-receptor were significantly higher inWT-IR-Sita and DPP4(D)-IR than those in other groups (all p <0.001). CONCLUSION: Abrogation of DPP4 activity protects against myocardial IR injury and preserved heart function.

Levels and values of lipoprotein-associated phospholipase A2, galectin-3, RhoA/ROCK, and endothelial progenitor cells in critical limb ischemia: pharmaco-therapeutic role of cilostazol and clopidogrel combination therapy.

OBJECTIVE: We tested the hypothesis that clopidogrel and cilostazol combination therapy could effectively attenuate systemic inflammatory reaction, facilitate proliferation of circulating endothelial progenitor cell (EPC), and improve the clinical outcomes of critical limb ischemia (CLI) in patients unsuitable for surgical revascularization or percutaneous transluminal angioplasty (PTA). METHODS: A total 55 patients (mean age, 72 years; 56% female) were consecutively enrolled. Clopidogrel and cilostazol combination therapy was administered throughout the study period. RESULTS: As compared with the baseline, circulating endothelial progenitor cell level (as shown by flow cytometry) was significantly increased (p<0.003), whereas the CLI-related ulcers and painfulness were significantly improved (all p<0.01) by day 90 after treatment. On the other hand, after clopidogrel and cilostazol combination therapy, galectin-3 level, lipoprotein-associated phospholipase A2 gene expression, and RhoA/ROCK-related protein expression in peripheral blood mononuclear cells were significantly suppressed (all p<0.01). Eventually, by day 90, 5 patients (9.1%) died of other etiologies, 3 (5.5%) withdrew from the study, 6 (10.9%) required amputation, and the remaining 41 had satisfactory clinical improvement with complete wound healing in 9 (16.4%) patients. CONCLUSION: The results of the present study highlight that clopidogrel and cilostazol combination therapy may be considered to be an alternative method for treating patients with CLI unsuitable for surgical revascularization or PTA.