bluuebunny/crossref_metadata_2025 huggingface dataset:
Bank rescues and fiscal policy in the European Union during the great recession
Authors: Ferreiro Jesús , Gálvez Catalina , Gómez Carmen , González Ana
Published: May 2016

The outbreak of the economic and financial crisis in 2008, the socalled Great
Recession, has made that many European Union countries have made massive
interventions in their banking and financial systems. These interventions
have had a considerable impact in the public finances of these countries. The
aim of the paper is to analyze the impact on the national public budgets of
the measures of public support to problem financial institutions carried out
between the years 2008 and 2013, and to study how this budgetary impact has
affected to the fiscal imbalances and to the strategies of fiscal impulse and
consolidation implemented along these years.
Adrenomedullin Expression in the Developing Human Fetal Lung
Authors: Ramos Carlos G. , Sun Xi , Johnson Eric B. , Nelson Harold E. , Gonzalez Bosc Laura V.
Published: May 2016

Background

Adrenomedullin (AM) is a vasodilator peptide produced by endothelial and smooth muscle cells in the systemic and pulmonary circulation. It promotes angiogenesis and alveolar growth and has protective effects in the cardiovascular and respiratory systems. Adrenomedullin's role in human pulmonary vascular and alveolar development is unknown.

Objective

To test the hypothesis that AM is expressed during normal human lung development and that its expression changes with advancing gestational age by investigating the messenger RNA and protein expression of AM and its receptor components, calcitonin-receptorlike receptor (CRLR), receptor activity–modifying protein (RAMP)2, and RAMP3 in human fetal lung from 10 to 24 weeks of gestation.

Methods

The gene expression of AM, CRLR, RAMP2, and RAMP3 was measured with real-time reverse-transcription polymerase chain reaction. Adrenomedullin protein expression was measured with Western blot. Immunohistochemical analyses of sections of lung tissue were performed. Statistical analysis was performed using linear regression and one-way analysis of variance followed by the Tukey range test.

Results

Adrenomedullin, CRLR, RAMP2, and RAMP3 transcripts were expressed in the midgestation human fetal lung. The gene expression of AM, CRLR, and RAMP2 increased with increasing gestational age, whereas the gene expression of RAMP3 decreased. Adrenomedullin protein expression increased with increasing gestational age.

Conclusion

Adrenomedullin is expressed in the midgestation human fetal lung and its gene and protein expression increased with increasing gestational age, suggesting a role for AM in human lung development. Supporting this conclusion, the AM1 receptor components CRLR and RAMP2 gene expression also increased with increasing gestational age. Conversely, the expression of RAMP3, a structural component of the AM2 receptor, decreased with increasing gestational age, suggesting different functions for the AM receptors in human fetal lung, as it has been demonstrated in animal models. This speculation requires further investigation.
A Shift in the Balance of Regulatory T and T Helper 17 Cells in Rheumatic Heart Disease
Authors: Bas Hatice Duygu , Baser Kazim , Yavuz Emine , Bolayir Hasan Ata , Yaman Belma , Unlu Serkan , Cengel Atiye , Bagriacik Emin Umit , Yalcin Ridvan
Published: May 2016

Background

Autoimmunity plays an essential role in the pathogenesis of rheumatic heart disease (RHD); however, cellular mechanisms of autoimmune response are unclear. Whereas T helper 17 (TH17) and regulatory T cells (Treg) cells share a common differentiation pathway, they play opposite roles in the immune tolerance and autoimmune diseases. Although high TH17/Treg ratio has been shown in several autoimmune diseases, no data are available in RHD. This study investigated the balance between TH17 and Treg in rheumatic mitral valve disease (MVD).

Methods

Forty patients with rheumatic MVD and 23 control subjects were enrolled into the study. All subjects underwent clinical, electrocardiographic, and echocardiographic evaluation. The percentages of circulating TH17 and Treg cells were analyzed by flow cytometry. Serum levels of high-sensitivity C-reactive protein (hs-CRP) and cytokines were assessed by enzyme-linked immunosorbent assay.

Results

As compared with control subjects, rheumatic MVD patients showed significant increase in peripheral TH17 percentage, high serum levels of TH17-related cytokine interleukin 17A, and an obvious decrease in the percentage of Treg cells. T helper 17/Treg ratio was significantly high in rheumatic MVD patients compared with control subjects ( P = 0.0001). Serum concentrations of hs-CRP in rheumatic MVD group were higher than those of the control subjects, and hs-CRP levels correlated with the TH17/Treg ratio ( r = 0.71, P = 0.0001). Serum levels of transforming growth factor β1 were increased in rheumatic MVD group compared with those of the control subjects.

Conclusions

The results indicated that high TH17/Treg ratio exists inrheumatic MVD. This imbalance may play a role in the pathogenesis, and TH17/Treg balance may be a promising therapeutic approach in RHD.
Tobacco Smoke–Induced Immunologic Changes May Contribute to Oral Carcinogenesis
Authors: Schierl Michael , Patel Daxesh , Ding Wanhong , Kochhar Amit , Adhami Katayun , Zhou Xi Kathy , Dannenberg Andrew J. , Granstein Richard D.
Published: May 2016

Objective

The objective of this study was to determine if tobacco smoke (TS), a risk factor for cancers of the aerodigestive tract, may contribute to oral carcinogenesis, in part, by suppressing local immunity.

Methods

Mice were placed in Plexiglas holders in which they breathed TS through the nose and mouth for 1 hour daily for 21 days. Control mice breathed room air in the same manner. One day after the last exposure, mice were immunized by application of oxazolone to each buccal mucosa. Control mice were mock immunized by application of vehicle alone. Five days later, all mice were challenged on the ears with oxazolone, and 24-hour ear swelling assessed as contact hypersensitivity.

Results

Mice exposed to TS had a significantly smaller contact hypersensitivity response compared with controls. When subsequently reimmunized on the glabrous skin, mice originally primed through TS-exposed mucosa could not be fully immunized, indicating induction of immunologic tolerance by exposure to hapten through TS-perturbed mucosa. Immunocompetent mice exposed to TS in this manner and challenged by submucosal placement of a syngeneic malignant tumor had significantly increased tumor growth over time compared with controls. No difference in growth rate was observed when the experiment was performed with natural killer cell–deficient, SCID (severe combined immunodeficiency) mice. In addition, exposure of epidermal Langerhans cells in vitro to an aqueous extract of TS impaired their ability to undergo maturation and to present antigen to responsive T cells.

Conclusions

Immunologic changes induced in the oral cavity by exposure to TS may play a role in the development of oral cancers.
Importance of Biomarkers in Risk Stratification of Pulmonary Thromboembolism Patients
Authors: Babaoglu Elif , Hasanoglu H. Canan , Senturk Aysegul , Karalezli Aysegul , Kilic Hatice , Aykun Gokhan , Oztuna Derya
Published: May 2016

Introduction

Patients with pulmonary thromboembolism (PTE) are classified into 3 groups according to the clinical risk factors associated with mortality. High-risk patients and some of the intermediate-risk patients should be treated immediately to decrease the high mortality risk. Although clinical risk level of PTE can be determined by using echocardiography to evaluate right ventricle overload and pulmonary artery pressure findings, it may not be available in all emergency settings.

Aim

The purpose of the study was to define the laboratory biomarkers, which can be used in place of echocardiography for PTE risk stratification.

Methods

Patients (n = 98) were divided into 3 groups as high-risk (n = 13), intermediate-risk (n = 50), and low-risk (n = 35) groups, according to clinical risk factors at the first referral to hospital. Hepatic, cardiac, and renal markers were evaluated and compared among 3 groups.

Results

Among biomarkers examined, lactate dehydrogenase, urea, creatinine, uric acid, troponin I, N-terminal–pro–B-type natriuretic peptide, creatine kinase–MB, D-dimer, and erythrocyte sedimentation rate (ESR) levels were found different between groups. All of these biomarkers except for ESR had positive correlation, whereas ESR had negative correlation with the mortality risk. An analysis of covariance for the age difference among patient groups showed that all the biomarkers other than urea and D-dimer levels remained significantly different among risk groups.

Conclusions

At emergency conditions in which echocardiography assessment is not available, PTE patients who have increased levels of certain hepatic, cardiac, and renal biomarkers should cautiously be evaluated for having an increased risk for mortality. Increased levels of these biomarkers may guide the consideration for thrombolytic treatment.
Effect of Prostaglandin I2 Analogs on Macrophage Inflammatory Protein 1α in Human Monocytes via I Prostanoid Receptor and Cyclic Adenosine Monophosphate
Authors: Tsai Ming-Kai , Hsieh Chong-Chao , Kuo Hsuan-Fu , Yang San-Nan , Kuo Chang-Hung , Huang Ming-Yii , Tsai Ying-Ming , Lee Min-Sheng , Hung Chih-Hsing
Published: May 2016

Aims

Inflammation plays critical roles in atherosclerosis. Chemokines are responsible for leukocyte trafficking and involve in inflammatory diseases. Macrophage inflammatory protein 1α (MIP-1α) has been implicated in atherosclerotic lesion formation. Prostaglandin I2 (PGI2) analog, used in pulmonary hypertension, has been reported to have anti-inflammatory functions. However, little is known about its role in the MIP-1α production in human monocytes.

Methods

We investigated the effects of 3 conventional (iloprost, beraprost, and treprostinil) and 1 new (ONO-1301) PGI2 analogs, on the expression of MIP-1α expression in human monocytes. Human primary monocytes from control subjects and THP-1 cell line were treated with PGI2 analogs, with or without lipopolysaccharide (LPS) stimulation. Supernatants were harvested to measure MIP-1α levels by enzyme-linked immunosorbent assay. To explore which receptors involved the effects of PGI2 analogs on the expression of MIP-1α expression, I prostanoid (IP) and E prostanoid, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-r receptor antagonists were used to pretreat THP-1 cells. Forskolin, a cyclic adenosine monophosphate (cAMP) activator, was also used to further confirm the cAMP involvement on the effect of PGI2 analogs in MIP-1α production.

Results

Three PGI2 analogs could suppress LPS-induced MIP-1α production in THP-1 cells and human primary monocytes. ONO-1301 had a similar effect. CAY 10449, an IP receptor antagonist, could reverse the suppressive effects on MIP-1α production of iloprost. Forskolin, a cAMP activator, also suppressed MIP-1α production in THP-1 cells.

Conclusions

Prostaglandin I2 analogs suppressed LPS-induced MIP-1α production in human monocytes via the IP receptor and cAMP pathway. The PGI2 analog may be potential in the treatment for atherosclerosis.
The Rationale/Design of the Guimarães/Vizela Study: A Multimodal Population-Based Cohort Study to Determine Global Cardiovascular Risk and Disease
Authors: Cunha Pedro Guimarães , Cotter Jorge , Oliveira Pedro , Vila Isabel , Sousa Nuno
Published: May 2016

Background

Cardiovascular disease and dementia are growing medical and social problems in aging societies. Appropriate knowledge of cardiovascular disease and cognitive decline risk factors (RFs) are critical for global CVR health preventive intervention. Many epidemiological studies use case definition based on data collected/measured in a single visit, a fact that can overestimate prevalence rates and distant from clinical practice demanding criteria. Portugal displays an elevated stroke mortality rate. However, population's global CV risk characterization is limited, namely, considering traditional/nontraditional RF and new intermediate phenotypes of CV and renal disease. Association of hemodynamic variables (pulse wave velocity and central blood pressure) with global CVR stratification, cognitive performance, and kidney disease are practically inexistent at a dwelling population level.

Study Design and Methods

After reviewing published data, we designed a population-based cohort study to analyze the prevalence of these cardiovascular RFs and intermediate phenotypes, using random sampling of adult dwellers living in 2 adjacent cities. Strict definition of phenotypes was planned: subjects were observed twice, and several hemodynamic and other biological variables measured at least 3 months apart.

Results

Three thousand thirty-eight subjects were enrolled, and extensive data collection (including central and peripheral blood pressure, pulse wave velocity), sample processing, and biobank edification were carried out. One thousand forty-seven cognitive evaluations were performed.

Conclusions

Seeking for CV risk reclassification, early identification of subjects at risk, and evidence of early vascular aging and cognitive and renal function decline, using the strict daily clinical practice criteria, will lead to better resource allocation in preventive measures at a population level.
Are Human Adenovirus-5 and 36 Associated with Obesity in Children?
Authors: Cakmakliogullari Elcin Kal , Sanlidag Tamer , Ersoy Betul , Akcali Sinem , Var Ahmet , Cicek Candan
Published: May 2016

Objectives

The aims of this study were to determine the association between adenovirus-5– and adenovirus-36–specific antibodies and obesity in children and to investigate their relationship with serum lipid and leptin levels.

Methods

A cross-sectional study was performed on a total of 120 children who were divided into subgroups according to body mass index percentile as obese (≥95th percentile) or nonobese (<95th percentile). The presence of adenovirus-36 and adenovirus-5–neutralizing antibodies was investigated by using the serum neutralization assay. Serum leptin levels were determined by microenzyme immonoassay; high-density lipoprotein, low-density lipoprotein, triglyceride, and cholesterol levels were measured by chemiluminescence method.

Results

The presence of adenovirus-5–specific antibodies was 28.3% and 6.6% in the obese children and in non–obese children, respectively ( P = 0.02). The frequency of adenovirus-36–specific antibodies was significantly greater ( P = 0.018) in the obese children (26.6%) than in the non–obese children (10.0%). Serum leptin level of the obese group were significantly higher than that of the non–obese group ( P = 0.000).

Conclusions

Our data support the association between obesity and the presence of specific antibodies to adenovirus-36 and adenovirus-5 in children. Our research has the feature of being the first national study to indicate the relationship between adenovirus-36 and human obesity as well as the first international study to indicate the relationship between adenovirus-5 and human obesity.
Prediction of Cerebrovascular and Cardiovascular Events in Patients with Subclinical Carotid Atherosclerosis
Authors: Rizzo Manfredi , Corrado Egle , Coppola Giuseppe , Muratori Ida , Novo Salvatore
Published: May 2016

Background

Several studies have suggested that inflammation and infection may be important for accelerated progression of atherosclerosis, but few data are available on subjects with early stages of atherosclerosis.

Methods and Results

We included, in a prospective 5-year follow-up study, 150 patients with subclinical carotid atherosclerosis, evaluating at baseline all established traditional cardiovascular risk factors (eg, older age, male sex, obesity, hypertension, diabetes, smoking, family history of coronary artery disease, and dyslipidemia); 2 markers of inflammation, fibrinogen, and high-sensitivity C-reactive protein (CRP); and the seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus. After follow-up, cardiovascular and cerebrovascular events were registered in the 19% of patients, and the increment in CRP levels (in quintiles) was significantly associated with ischemic stroke ( P = 0.0253), acute myocardial infarction ( P = 0.0055), cardiovascular or cerebrovascular death ( P = 0.0145), and the presence of any event ( P = 0.0064). Most traditional cardiovascular risk factors (eg, older age, hypertension, diabetes, and dyslipidemia) were significantly associated with the events but only in the unadjusted analysis; in fact, at logistic regression analysis, among all baseline variables, only elevated CRP levels showed a predictive role (odds ratio, 7.0; 95% confidence interval, 2.2-18.4; P = 0.0247).

Conclusions

Our findings suggest that elevated CRP concentrations may significantly influence the occurrence of cerebrovascular and cardiovascular events in patients with baseline subclinical carotid atherosclerosis. Notably, null findings were obtained by viral and bacteria titers, suggesting a greater role of inflammation (and not of infection) in the progression of atherosclerosis in our cohort. However, further studies are needed to evaluate the therapeutic implications in this category of patients.
The Role of PPARγ in Pulmonary Vascular Disease
Authors: Hart C. Michael
Published: May 2016

The peroxisome proliferator-activated receptor (PPAR) γ is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Thiazolidinediones, pharmacological ligands for PPARγ, are currently used in the management of type 2 diabetes. Peroxisome proliferator-activated receptor γ is expressed in the lung and pulmonary vasculature, and its expression is reduced in the vascular lesions of patients with pulmonary hypertension. Furthermore, thiazolidinedione PPARγ ligands reduced pulmonary hypertension and vascular remodeling in several experimental models of pulmonary hypertension. This report reviews current evidence that PPARγ may represent a novel therapeutic target in pulmonary hypertension and examines studies that have begun to elucidate mechanisms that underlie these potential therapeutic effects.
Oxidative DNA Damage is Significantly Correlated with Flow-Mediated Dilation in Patients with Coronary Artery Disease
Authors: Yurdakul Selen , Ozben Beste , Bilge Ahmet Kaya , Turkoglu Umit Mutlu , Arkaya Selda , Nisanci Yilmaz
Published: May 2016

Background

Oxidative DNA damage was increased in patients with coronary artery disease (CAD) and correlated with the severity of the disease. Endothelial dysfunction plays a major role in atherosclerotic process. The aim of this study was to explore a relation between oxidative DNA damage and endothelial function in patients with CAD.

Methods

Forty patients with CAD and 20 age- and sex-matched healthy controls were included. Endothelial function was assessed by brachial artery ultrasonography. The DNA damage was determined by comet method.

Results

The DNA damage scores after incubation with repair enzymes were found significantly higher in the patients with CAD ( P = 0.04). There was a significant negative correlation between oxidized DNA damage scores and flow-mediated dilation (FMD) measures in the patients with CAD ( r = −0.41; P = 0.009). Oxidized DNA damage scores were significantly and independently associated with FMD (standardized β = −0.455; P = 0.009) when adjusted by age, sex, smoking status, blood pressure, and cholesterol levels.

Conclusions

The DNA damage scores were significantly inversely correlated with FMD measures. To our knowledge, this is the first study showing the presence of a relation between DNA damage scores and FMD.
Non-High-Density Lipoprotein Cholesterol in Patients with Metabolic Syndrome
Authors: Huang Jian , Parish Roy , Mansi Ishak , Yu Herbert , Kennen Estela M. , Davis Terry , Carden Donna
Published: May 2016

Background

Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors that includes hypertriglyceridemia. Although low-density lipoprotein (LDL) cholesterol is the critical therapeutic target in patients with coronary artery disease, LDL cannot be calculated in those with excessive hypertriglyceridemia. Non-high-density lipoprotein (HDL) does not require LDL for calculation and may be an alternative therapeutic target in MS. The purpose of this study was to determine non-HDL cholesterol in relation to other lipid components and comorbidities in MS patients.

Methods

A cross-sectional chart review on 928 public hospital patients was performed.

Results

Metabolic syndrome was present in 53% of all patients. Among those with MS, 87% had triglyceride level of greater than 150 mg/dL, 85% had low HDL, 71% had LDL of greater than 100 mg/dL, and 74% had non-HDL of greater than 130 mg/dL. The level of non-HDL cholesterol, but not total cholesterol or LDL cholesterol, was significantly higher ( P < 0.05) and less at goal ( P < 0.0001) in patients with MS. Diagnoses of coronary artery disease, hypertension, obesity, dyslipidemia, and diabetes were significantly more prevalent in MS patients ( P < 0.0001).

Conclusion

Compared with those without MS, non-HDL level was significantly higher and undertargeted in patients with MS, in parallel with significantly higher prevalence of comorbidities.
Perioperative Risk of Patients Undergoing Noncardiac Surgery after Coronary Artery Bypass Surgery
Authors: Daye Jad , Boatman Dustin , Peters Calvin , Varghese Indu , Haider Aman , Roesle Michele , Jessen Michael E. , DiMaio J. Michael , Banerjee Subhash , Brilakis Emmanouil S.
Published: May 2016

Background

Most data suggesting that noncardiac surgery early after coronary artery bypass surgery carries low risk are derived from post hoc analyses of randomized controlled trials, with only limited data derived from contemporary, nonselected, and nontrial patients.

Methods

We retrospectively reviewed the medical records of patients who underwent coronary artery bypass surgery at our institution between January 1999 and October 2006 to determine whether they subsequently had major noncardiac surgery and what the outcomes of the noncardiac surgery were.

Results

During the study period, 1065 patients underwent coronary artery bypass surgery, and 272 (26%) subsequently underwent 467 major noncardiac surgeries. The mean interval from coronary artery bypass to noncardiac surgery was 1.9 ± 1.9 years (range, 0-7.8 years). A major complication occurred in 3 surgeries (0.6% [95% confidence interval, 0.1%-1.9%]). Two patients died (both from respiratory arrest during the postoperative period: 1 patient had a tongue cancer excision, and the other patient had polycythemia vera), and the third patient had a perioperative arrhythmia.

Conclusions

Noncardiac surgery is often required early after coronary artery bypass surgery and carries very low risk for cardiac complications, suggesting that preoperative cardiac evaluation may not be required in most such patients.
Inducible Nitric Oxide Synthase Inhibitor SD-3651 Reduces Proteinuria in MRL/lpr Mice Deficient in the NOS2 Gene
Authors: Njoku Chinedu , Self Sally E. , Ruiz Philip , Hofbauer Ann F. , Gilkeson Gary S. , Oates Jim C.
Published: May 2016

Several studies have demonstrated the effectiveness of arginine analog nitric oxide synthase (NOS) inhibitor therapy in preventing and treating murine lupus nephritis. However, MRL/MpJ- FASlpr(MRL/lpr) mice lacking afunctional NOS2 (inducible NOS [iNOS]) gene (NOS2−/−) develop proliferative glomerulonephritis in a fashion similar to their wild-type (wt) littermates. This finding suggests that the effect of arginine analog NOS inhibitors is through a non-iNOS-mediated mechanism. This study was designed to address this hypothesis.

NOS2−/− mice were given either vehicle or a NOS inhibitor (SD-3651) to determine if pharmacological NOS inhibition prevented glomerulonephritis, using wt mice as positive controls. Urine was collected fortnightly to measure albumin. At the time of full disease expression in wt mice, all mice were killed, and renal tissue was examined for light, immunofluorescence, and electron microscopic evidence of disease. Serum was analyzed for anti-double-stranded DNA antibody production.

NOS2−/− mice had higher serum anti-double-stranded DNA antibody antibody levels than those of wt mice. SD-3651 therapy reduced proteinuria, glomerular immunoglobulin G deposition, and electron microscopic evidence of podocytopathy and endothelial cell swelling without affecting proliferative lesions by light microscopy.

These studies confirm that genetic iNOS deficiency alone is insufficient to prevent proliferative glomerulonephritis and suggest that iNOS activity may inhibit autoantibody production. These results also suggest that SD-3651 therapy acts via a non-iNOS-mediated mechanism to prevent endothelial cell and podocyte pathology. Studies that elucidate this mechanism could provide a useful drug target for the treatment of nephritis.
Oxandrolone Enhances Hepatic Ketogenesis in Adult Men
Authors: Vega Gloria Lena , Clarenbach Jacob J. , Dunn Fredrick , Grundy Scott M.
Published: May 2016

Background

Immediate administration of oxandrolone markedly increases hepatic lipase activity and reduces levels of plasma high-density lipoprotein.

Rationale for the study

We postulated that oxandrolone should increase hepatic lipase and that the nonesterified fatty acids generated would enhance hepatic ketogenesis during an extended fat tolerance test.

Main Results

Eighteen men participated in the study using short-term administration of oxandrolone (10 mg/d) over a week. Subjects had evaluation of hepatic ketogenesis at baseline and after 7 days of administration of oxandrolone. Ketogenesis was assessed by measuring plasma levels of 3-hydroxybutyrate during a fat tolerancetest. Oxandrolone increased fasting levels of 3-hydroxybutyrate by 70%, and increased the area under the curve during an FFT by 53% above pretreatment levels without affecting the areas under the curve for nonesterified fatty acids, glycerol, or triglycerides. Fasting 3-hydroxybutyrate levels correlated with nonesterified fatty acids and with triglycerides; however, there were no significant correlations with any other parameter.

Conclusions

This study shows that short-term administration of oxandrolone results in marked increases in hepatic ketogenesis. This finding is consistent with an increased influx of fatty acids into the liver secondary to lipoprotein lipolysis by increased hepatic lipase. However, the possibility cannot be ruled out that oxandrolone acts directly in the liver to stimulate fatty acid oxidation. Therefore, the observation of increased ketogenesis will require further studies to determine the molecular basis of the response.
Continuous Inhaled Nitric Oxide Therapy in a Case of Sickle Cell Disease with Multiorgan Involvement
Authors: Chang Wun-Ling , Corate Lalaine M. , Sinclair James M. , van der Heyde Henri C.
Published: May 2016

A 27-year-old female with sickle cell disease (HbSS) was admitted presenting with severe bone pain and fever. She refused blood transfusions throughout her hospital stay for religious reasons. During the first 9 days of admission, the patient's clinical presentation became worse despite antibiotic coverage. The patient exhibited pulmonary infiltrates and mild hypertension, increased pain, fever, tachycardia, and decreased hematocrit. After day 8 of admission, her laboratory findings and clinical presentation indicated that her disease was markedly worse. With the patient's consent, inhaled nitric oxide therapy (iNO = 40 ppm) was initiated and continued for 3.2 days. After a full day of iNO therapy, the clinical improvement was limited to temperature normalization and stabilization of her hemoglobin levels. After 2 more days of iNO therapy, her multiple clinical complications of sickle cell disease improved markedly and she was discharged 3 days after completion of the iNO treatment. The complications of NO therapy, such as methemoglobulinemia or decreased blood pressure, were not detected during the iNO therapy. Although limited to a single individual, we propose that our anecdotal experience suggests that iNO therapy may (i) need to be continuous for several days to provide improved benefits, (ii) treat several of sickle cell complications besides pain, and (iii) exhibit few complications. These proposals need to be confirmed in clinical trials.
Harbingers for Clostridium difficile-Associated Diarrhea
Authors: Pant Chaitanya , Madonia Phillip N. , Jordan Paul , Manas Kenneth , Bass Pat
Published: May 2016

Purpose

Recent research has recognized surrogate markers for Clostridium difficile-associated diarrhea (CDAD). Among the most consistently identified markers are the leukocyte count, platelet count, and albumin level. Previous investigators failed to exclude patients with hematologic disorders that may have confounded their results. Therefore, the exclusion of this subset from our study lends it a unique perspective.

Methods

We undertook a retrospective review of inpatients at our institution that were diagnosed with nosocomial diarrhea and subsequently had a stool sample sent for C. difficile toxins A and B. Patients with major hematologic disorders were excluded.

Results

A total of 77 C. difficile-positive patients and 91 C. difficile-negative patients were studied. Patients with CDAD had a significantly higher leukocyte and platelet count but a lower albumin level compared with patients without CDAD.

Conclusion

Our results support the conclusion of preceding studies that leukocytosis, thrombocytosis, and hypoalbuminemia are reliable clinical predictors for CDAD even after careful exclusion of confounding factors.
Collaborative Care Interventions for Depression in the Elderly
Authors: Chang-Quan Huang , Bi-Rong Dong , Zhen-Chan Lu , Yuan Zhang , Yu-Sheng Pu , Qing-Xiu Liu
Published: May 2016

Objective

To determine the effective components and the feasibility of collaborative care interventions (CCIs) in the treatment of depression in older patients.

Methods

Systematic review of randomized controlled trials, in which CCIs were used to manage depression in patients aged 60 or older.

Results

We identified 3 randomized controlled trials involving 3930 participants, 2757 of whom received CCIs and the others received usual care. Collaborative care interventions were more effective in improving depression symptoms than usual care during each follow-up period. Compared with baseline, thoughts of suicide in subjects receiving CCIs significantly decreased (odds Ratio [OR], 0.52; 95% confidence intervals [CI], 0.35−0.77), but not that in those receiving usual care (OR, 0.85; 95% CI, 0.50−1.43). Subjects receiving CCIs were significantly more likely to report depression treatment (including any antidepressant medication and psychotherapy) than those receiving usual care during each follow-up period. Collaborative care interventions significantly increased depression-free days, but did not significantly increase outpatient cost. At 6 and 12 months postintervention, compared with those receiving usual care, participants receiving CCIs had lower levels of depression symptoms and thoughts of suicide. Moreover, participants receiving CCIs were significantly more likely to report antidepressant medication treatment, but were not significantly more likely to report psychotherapy. Collaborative care interventions with communication between primary care providers and mental health providers were no more effective in improving depression symptoms than CCIs without such communication.

Conclusions

Collaborative care interventions are more effective for depression in older people than usual care and are also of high value. Antidepressant medication is a definitely effective component of CCIs, but communication between primary care providers and mental health providers seems not to be an effective component of CCIs. The effect of psychotherapy in CCIs should be further explored.
Matrix Metalloproteinases Gene Variants in Idiopathic Disseminated Bronchiectasis
Authors: Stankovic Marija , Nikolic Aleksandra , Divac Aleksandra , Rakicevic Ljiljana , Tomovic Andrija , Mitic-Milikic Marija , Nagorni-Obradovic Ljudmila , Grujic Milan , Petrovic-Stanojevic Natasa , Andjelic-Jelic Marina , Dopudja-Pantic Vesna , Radojkovic Dragica
Published: May 2016

Background

The excess of matrix metalloproteinases (MMPs) might be associated with the airways destruction or dilatation in bronchiectasis. The functional promoter polymorphisms of MMP1 and MMP9 genes, involved in the extracellular matrix remodeling, might increase the expression of MMPs leading to the development of bronchiectasis.

Methods

Detection of MMP1 G-1607GG and MMP9 C-1562T gene variants was performed on 37 patients with idiopathic disseminated bronchiectasis and 102 control subjects. We also described a novel method for simple and rapid detection of MMP1 G-1607GG polymorphism.

Results

The frequency of -1607GG allele was significantly higher in the group of patients than in control subjects ( P = 0.014). The heterozygote genotype showed association with bronchiectasis (odds ratio, 5.3; 95% confidence intervals, 1.4-20.0). The association was even stronger in homozygotes for -1607GG allele (odds ration, 8.7; 95% confidence intervals, 1.9-41.0). The allelic and genotype frequencies of MMP9 C-1562T variant did not show significant differences between the groups.

Conclusions

This is the first report concerning a role of MMP1 G-1607GG and MMP9 C-1562T variants in pathogenesis of idiopathic disseminated bronchiectasis. The results of our study revealed the association of -1607GG allele and the lack of association of MMP9 C-1562T variant with the disease.
Oxidative DNA Damage and Antioxidant Defense after Reperfusion in Acute Myocardial Infarction
Authors: Himmetoglu Solen , Dincer Yildiz , Bozcali Evin , Ali Vural Vural , Akcay Tulay
Published: May 2016

Purpose

Myocardial damage mediated by oxidative stress during acute myocardial infarction (MI) has been suggested as an obstructive factor on recovery after an MI. 8-Hydroxydeoxyguanosine (8-OHdG) is a marker for oxidative DNA damage; superoxide dismutase (SOD) and glutathione peroxidase (G-Px) are major antioxidant enzymes. We determined changes in the plasma level of 8-OHdG and activities of SOD and G-Px in patients with MI and examined the relations between those changes and other cardiac markers.

Methods

Blood samples were taken at the beginning of the therapy, on the third day of hospitalization, and on the day patients were discharged home. Plasma level of 8-OHdG and SOD and G-Px activities were measured by enzyme-linked immunosorbent assay and spectrophotometric kits, respectively.

Results

8-Hydroxydeoxyguanosine level at the beginning of the therapy was found to be decreased on the third day of therapy and on the day patients were discharged home. With respect to the treatment way, 8-OHdG level was found to be slightly decreased on the third day of therapy and then remained stable in the group treated with thrombolytic agents. However, 8-OHdG level was found to be sharply decreased on the third day of therapy in the group that underwent primary percutaneous transluminal coronary angioplasty. No significant relations were determined between those measured parameters and serum levels of cardiac markers.

Conclusion

Although not correlated with other cardiac markers, plasma level of 8-OHdG shows a decrease after reperfusion therapy in patients with MI, and primary percutaneous transluminal coronary angioplasty seems much more effective than thrombolytic therapy for providing a low level of 8-OHdG.
Use of Short-Radius Centrifugation to Augment Ankle-Brachial Indices
Authors: Grenon S. Marlene , Mateus Jaime , Hsiang York , Sidhu Ravi , Young Laurence , Gagnon Joel
Published: May 2016

Background

Peripheral arterial disease is mainly caused by atherosclerosis and is characterized by decreased circulation, lower blood pressure, and insufficient tissue perfusion in the lower extremities. The hemodynamics of standing and altered gravity environments have been well studied relative to arm blood pressures but are less well understood for ankle pressures.

Methods

Because regional blood pressure depends, in part, on the gravitational pressure gradient, we hypothesized that artificial gravity exposure on a short-arm centrifuge with the center of rotation above the head would increase blood pressure in the lower extremities. Cardiovascular parameters for 12 healthy subjects were measured during exposure to supine short-arm centrifugation at 20, 25, and 30 revolutions per minute (rpm), corresponding to centripetal accelerations of 0.94, 1.47, and 2.11 Gz at the foot level, respectively.

Results

Systolic ankle blood pressure significantly increased at all levels of centrifugation. Ankle-brachial indices (the ratio of systolic ankle to arm blood pressures) increased significantly from 1.17 ± 0.03 to 1.58 ± 0.03 at 0.94 Gz ( P < 0.005), 1.74 ± 0.02 at 1.47 Gz ( P < 0.005), and 1.89 ± 0.06 at 2.11 Gz ( P < 0.005). Systolic arm blood pressure significantly increased at 2.11 Gz, but heart rate did not change significantly. All parameters returned to normal after cessation of centrifugation.

Conclusions

We demonstrated that short-radius centrifugation leads to an increase in ankle-brachial indices. This could have potential implications for the treatment of peripheral arterial disease.
DNA Oxidation and Antioxidant Status in Breast Cancer
Authors: Himmetoglu Solen , Dincer Yildiz , Ersoy Yeliz E. , Bayraktar Bariş , Celik Varol , Akcay Tulay
Published: May 2016

Purpose

Oxidant/antioxidant balance has been suggested as an important factor for initiation and progression of cancer. The objective of this study was to determine 8-hydroxydeoxyguanosine (8-OHdG) level as a marker of oxidative DNA damage, glutathione peroxidase (G-Px), and superoxide dismutase (SOD) activities as antioxidant activity, in sera from women with breast cancer.

Methods

Forty-nine patients with malign breast tumor were included in the study. Blood samples were collected before the surgical operation. Serum level of 8-OHdG was measured with a competitive enzyme-linked immunusorbent assay kit, SOD, and G-Px activities were measured by spectrophotometric kits.

Results

8-Hydroxydeoxyguanosine level and SOD activity were found to be increased in breast cancer group as compared with control group. Glutathione peroxidase activity in the breast cancer group was lower than those in the control group. The ratio of 8-OHdG/G-Px in breast cancer patients was found to be higher than those in the controls. There were correlations between 8-OHdG and CA19-9 ( r = 0.77; P < 0.01); age and G-Px ( r = −0.84; P < 0.05) in the breast cancer group.

Conclusions

Data show that serum levels of 8-OHdG and SOD activities are higher in patients with breast cancer. Glutathione peroxidase activity is lower in the breast cancer group. Increased ratio of 8-OHdG/G-Px in breast cancer patients is the evidence for impaired oxidant/ antioxidant balance in breast cancer.
Variability in the Response to Cyclooxygenase Inhibitors: Toward the Individualization of Nonsteroidal Anti-Inflammatory Drug Therapy
Authors: Grosser Tilo
Published: May 2016

Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain, inflammation, and fever by inhibiting cyclooxygenases (COXs). Nonsteroidal anti-inflammatory drugs selective for COX-2 were developed to inhibit the major enzymatic source of the prostaglandins that mediate pain and inflammation while sparing COX-1-derived prostaglandins that contribute dominantly to gastric cytoprotection. Indeed, such purpose-designed COX-2 inhibitors reduced the incidence of serious gastrointestinal adverse effects when compared with traditional NSAIDs; however, they confer a small but absolute cardiovascular hazard. The hazard might also extend to traditional NSAIDs, which are relatively selective for COX-2, such as diclofenac, meloxicam, and etodolac. The occurrence of complications and the therapeutic responses to individual NSAIDs may vary substantially from patient to patient. Exploitation of detectable variability in the biochemical response to NSAIDs may offer an approach to the personalization of the management of risk and benefit.
Glucocorticoid Efficacy in Asthma is Improved Tissue Remodeling Upstream of Anti-Inflammation
Authors: Freishtat Robert J. , Nagaraju Kanneboyina , Jusko William , Hoffman Eric P.
Published: May 2016

Synthetic glucocorticoids (GCs), such as prednisone, are among the most widely prescribed drugs worldwide and are used to treat many acute and chronic inflammatory conditions. The current paradigm of GC efficacy is that they are potent anti-inflammatory agents. Decreased inflammation in many disorders is thought to lead to decreased pathological tissue remodeling. However, this model has never been validated. In particular, improvements in inflammation have not been shown to improve the rate of lung function decline in asthma. Herein, we present an alternative paradigm, where GC efficacy is mediated through more successful tissue remodeling, with reduction in inflammation secondary to successful regeneration.
MUC7 Polymorphisms are Associated with a Decreased Risk of a Diagnosis of Asthma in an African American Population
Authors: Watson Alan M. , Ngor Wai-Man , Gordish-Dressman Heather , Freishtat Robert J. , Rose Mary C.
Published: May 2016

Purpose

Mucin glycoproteins contribute to lung pathophysiology in asthma. The protein backbone of mucin glycoproteins is encoded by specific MUC genes, which exhibit a high degree of polymorphisms that generate a variable number of tandem repeat (VNTR) domains. MUC7 typically encodes for 6 VNTRs, each with 23 amino acids. In a northern European cohort, a polymorphism encoding MUC7*5 (5-VNTR) is in 100% linkage disequilibrium with the single nucleotide polymorphism rs9982010 and associated with a decreased risk of being asthmatic and having better lung function. African Americans have a 5- to 10-fold increase in incidence of asthma relative to whites, who are believed to be partially associated with higher genetic susceptibility. Occurrence of the rs9982010 and MUC7 allelic frequencies was evaluated in inner-city African Americans to test their association with a diagnosis of asthma.

Methods

Genomic DNA, collected from a cohort of African American asthmatic subjects, was used to detect the MUC7 VNTR polymorphisms and to analyze the rs9982010 single nucleotide polymorphism.

Results

A logistic regression analysis showed that the MUC7*5-VNTR allele decreased the likelihood of a diagnosis of asthma (odds ratio, 0.173 [95% confidence interval, 0.041-0.737]; P < 0.018) and is not in a strong linkage disequilibrium with the rs9982010 ( r2 = 0.03; odds ratio, 66; confidence interval, 5.913-736.72). A novel MUC7*4-VNTR polymorphism, identified in an African American nonasthmatic individual, was linked to a structural rearrangement of the VNTR domain.

Conclusions

These data extend the association of MUC7*5 allelic polymorphisms and asthma to inner-city African Americans.
Emotional Stress and Tako-Tsubo Cardiomyopathy: Observations on 2 Distinct Clinical Phenotypes
Authors: Yaqub Yasir , Jenkins Leigh A. , Suarez Jose , Sutthiwan Piraon , Phy Michael , Nugent Kenneth M. , Kumar Ashwani
Published: May 2016

Background

Tako-tsubo syndrome is a transient cardiomyopathy usually precipitated by an acute emotional or physiological stress. Our study objectives were to review and analyze the impact of emotional stress on clinical variables, echocardiographic characteristics, and short-term outcomes in patients with tako-tsubo syndrome.

Methods

Retrospective chart review.

Results

Eleven patients presented with tako-tsubo syndrome (1 man and 10 women) during the 8-year period (January 2000 to January 2008). The patients were split into 2 groups, defined by presenting either after emotional stress (6/11, 54.5%) or after idiopathic/physical stress (5/11, 45.5%). The mean age was 53.8 (12.6) years. The mean peak troponin T level was 0.54 ng/mL (range, 0.03-2.06 ng/mL), and the mean left ventricular end-diastolic pressure was 15.8 (8.1) mm Hg. Emotional stress was associated with younger age ( P = 0.024), a lower left ventricular end-diastolic pressure ( P < 0.05), more ST segment changes on electrocardiogram (66.7% vs 40%), and a higher ejection fraction ( P = 0.012). The patients in the idiopathic/physical stress group required more frequent hemodynamic support.

Conclusions

We conclude that clinical, echocardiographic, and outcome characteristics can differentiate tako-tsubo patients presenting with emotional stress from those with idiopathic/physical stress into 2 distinct clinical phenotypes. Clinicians should monitor idiopathic/physically stressed tako-tsubo patients carefully for hemodynamic compromise.
Randomized Clinical Trials in Stroke Research
Authors: Ahn Chul , Ahn Daniel
Published: May 2016

A randomized clinical trial is widely regarded as the most rigorous study design to determine the efficacy of intervention because spurious causality and bias associated with other experimental designs can be avoided. The purpose of this article is to provide clinicians and clinical researchers the types of randomized clinical trials used in stroke studies and to discuss the advantages and the limitations for each type of randomized stroke clinical trials.
Technical and Policy Approaches to Balancing Patient Privacy and Data Sharing in Clinical and Translational Research
Authors: Malin Bradley , Karp David , Scheuermann Richard H.
Published: May 2016

Introduction

Clinical researchers need to share data to support scientific validation and information reuse and to comply with a host of regulations and directives from funders. Various organizations are constructing informatics resources in the form of centralized databases to ensure reuse of data derived from sponsored research. The widespread use of such open databases is contingent on the protection of patient privacy.

Methods

We review privacy-related problems associated with data sharing for clinical research from technical and policy perspectives. We investigate existing policies for secondary data sharing and privacy requirements in the context of data derived from research and clinical settings. In particular, we focus on policies specified by the US National Institutes of Health and the Health Insurance Portability and Accountability Act and touch on how these policies are related to current and future use of data stored in public database archives. We address aspects of data privacy and identifiability from a technical, although approachable, perspective and summarize how biomedical databanks can be exploited and seemingly anonymous records can be reidentified using various resources without hacking into secure computer systems.

Results

We highlight which clinical and translational data features, specified in emerging research models, are potentially vulnerable or exploitable. In the process, we recount a recent privacy-related concern associated with the publication of aggregate statistics from pooled genome-wide association studies that have had a significant impact on the data sharing policies of National Institutes of Health-sponsored databanks.

Conclusion

Based on our analysis and observations we provide a list of recommendations that cover various technical, legal, and policy mechanisms that open clinical databases can adopt to strengthen data privacy protection as they move toward wider deployment and adoption.