bluuebunny/crossref_metadata_2025 huggingface dataset:
Prostate Cancer, Comorbidity, and Participation in Randomized Controlled Trials of Therapy
Authors: Chao Herta H. , Mayer Tina , Concato John , Rose Michal G. , Uchio Edward , Kelly Wm Kevin
Published: May 2016

Background

Randomized controlled trials (RCTs) evaluate the potential benefits of chemotherapy regimens and guide clinical care for patients with cancer. Inclusion criteria for RCTs are usually stringent and may exclude many patients seen in clinical practice. Our objective was to determine the proportion of men with castrate-resistant prostate cancer (CRPC) in a clinical setting that would have been excluded from major phase 3 RCTs.

Methods

We reviewed eligibility criteria from 24 phase 3 clinical trials evaluating chemotherapy for CRPC active from January, 2004, through April, 2008. We created a common list of criteria used in at least 3 studies and separately considered the criteria from a prominent RCT (TAX 327). We applied these criteria to a population of patients with CRPC treated during 2004 to 2006 at the Veterans Affairs Connecticut Healthcare System.

Results

Among 106 patients with CRPC, 99 (93%) had complete medical records, and 45 (45%) of the 99 would have been excluded from RCTs. Common reasons for exclusion were abnormal laboratory values, other malignancies, and other serious medical conditions including cardiac disease.

Conclusions

Almost half of the CRPC patients examined in a clinical setting would have been ineligible for phase 3 RCTs, highlighting that such trials may not be applicable to general oncology practice.
Erythropoietin Markedly Attenuates Brain Infarct Size and Improves Neurological Function in the Rat
Authors: Yuen Chun-Man , Leu Steve , Lee Fan-Yen , Yen Chia-Hung , Lin Yu-Chun , Chua Sarah , Chung Sheng-Ying , Chai Han-Tan , Sheu Jiunn-Jye , Ko Sheung-Fat , Sun Cheuk-Kwan , Yip Hon-Kan
Published: May 2016

Background

The impact of epoetin beta (recombinant human erythropoietin) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) induced by distal left internal carotid artery occlusion was investigated.

Methods

Adult male Sprague-Dawley rats (n = 30) were categorized into group 2 (IS only) and group 3 (IS plus intraperitoneal erythropoietin 5000 IU/kg at 0, 12, and 24 hours after IS). Healthy Sprague-Dawley rats (n = 10) served as group 1.

Results

Analysis of brain tissues showed larger BIA in group 2 than in group 3 ( P < 0.001). Corner test identified highest frequency of left turn in group 2 ( P < 0.05). The mRNA expressions of Bax, caspase 3, interleukin 18, toll-like receptor 4, and plasminogen activator inhibitor 1 were highest, whereas Bcl-2 was lowest in group 2 ( P < 0.05). Lower CXCR4 and stromal cell-derived factor 1 expressions were noted in group 2 than in group 3 ( P < 0.01). Immunohistofluorescence staining showed lower expressions of CXCR4, stromal cell-derived factor 1, von Willebrand factor, and doublecortin with higher number of apoptotic nuclei in group 2 than in group 3 ( P < 0.001). Immunohistochemical staining demonstrated lower cellular proliferation and number of small vessels with higher glial fibrillary acid protein expression in group 2 than in group 3 ( P < 0.01).

Conclusions

Erythropoietin significantly limited BIA and improved sensorimotor dysfunction after acute IS.
Elevated Plasma Levels of Chemerin in Newly Diagnosed Type 2 Diabetes Mellitus with Hypertension
Authors: Yang Mengliu , Yang Gangyi , Dong Jing , Liu Ying , Zong Haihong , Liu Hua , Boden Guenther , Li Ling
Published: May 2016

Chemerin is a recently discovered metabolic regulator hormone. The pathophysiologic role of this hormone in humans remains unknown. In this study, we have compared plasma chemerin levels in patients with type 2 diabetes mellitus with or without hypertension and in control subjects. We also assessed the association of plasma chemerin with body composition and metabolic parameters in these subjects. Plasma chemerin levels were found to be markedly increased in patients with type 2 diabetes mellitus with hypertension as compared with patients with type 2 diabetes mellitus and normal controls ( P < 0.01). Multiple regression analysis showed that waist circumference, diastolic blood pressure, 2-hour plasma insulin after glucose overload, and HbA1c were independently related factors influencing plasma chemerin levels. The present work indicates the potential link of chemerin with the pathogenesis of insulin resistance, obesity, and metabolic syndrome.
Cardiac Involvement in Patients with Hematologic Malignancies
Authors: Allegra Alessandro , Alonci Andrea , Russo Sabina , Cannavò Antonino , Penna Giuseppa , D'Angelo Arianna , Bellomo Giacomo , Musolino Caterina
Published: May 2016

Authors have reviewed literature about the management of patients with cardiologic disease occurring secondary to hematologic pathology itself or its therapy, with a focus on infiltration of myocardium in acute and chronic leukemia, lymphoma, multiple myeloma, and hypereosinophilic syndrome. Moreover, they evaluated chemotherapy-associated toxicity, particularly for new drugs such as monoclonal antibody therapy, tyrosine kinase inhibitors, arsenic trioxide, bortezomib, and epigenetic therapy. In fact, cardiac toxicity may range from asymptomatic subclinical abnormalities, such as electrocardiographic changes and left ventricular ejection decline, to life-threatening events and lead to chemotherapy dose reduction and delay and, in some cases, for patients with severe side effects, discontinuation of treatment.

Finally, they discussed on the identification of early markers of cardiac injury and on cardiac stem cell therapy as a promising approach to facilitate myocardial regeneration.
P-Glycoprotein Transporter Expression on A549 Respiratory Epithelial Cells is Positively Correlated with Intracellular Dexamethasone Levels
Authors: Cohen Joanna S. , Benton Angela S. , Nwachukwu Fisayo , Ozedirne Tugba , Teach Stephen J. , Freishtat Robert J.
Published: May 2016

Background

Several mechanisms of glucocorticoid resistance in asthma have been proposed. P-glycoprotein (P-gp), a ubiquitous efflux transport protein, is associated with variability in the disposition of many drugs and interindividual variability in drug treatment response. This study was undertaken to determine the effect of P-gp expression on glucocorticoid efflux from airway epithelial cells.

Hypothesis

Decreasing respiratory epithelial P-gp expression in dexamethasone-exposed airway epithelial cells in vitro will increase intracellular dexamethasone concentration.

Methods

A549 lung epithelial cells, transfected with small interfering RNA (siRNA) targeted at messenger RNA for the gene encoding P-gp, were exposed to 100-nM dexamethasone for 15 minutes. Transfection efficiency of siRNA, P-gp expression, and intracellular dexamethasone were measured with flow cytometry.

Results

Cells transfected with both negative siRNA and siRNA targeted at P-gp exhibited a positive correlation of P-gp expression with intracellular dexamethasone. The mean ± SEM correlation coefficients were 0.78 ± 0.07 for cells transfected with negative siRNA and 0.79 ± 0.08 for cells transfected with siRNA targeted at P-gp.

Discussion

Contrary to our hypothesis, the positive correlation between P-gp expression and intracellular dexamethasone suggests that P-gp is not a primary transporter of glucocorticoids from airway epithelial cells. Increased P-gp expression is unlikely to be an important mechanism of glucocorticoid resistance in asthma.
C-Reactive Protein in Acute Pulmonary Embolism
Authors: Abul Yasin , Karakurt Sait , Ozben Beste , Toprak Ahmet , Celikel Turgay
Published: May 2016

Background

Right ventricular dysfunction and N-terminal proB-type natriuretic peptide (NT-proBNP) are established determinants of prognosis in acute pulmonary embolism (PE). The aim of the study was to investigate the prognostic value of C-reactive protein (CRP) in PE.

Methods

Fifty-six patients (mean age, 64.4 ± 14.8years; 22 male subjects) with acute PE were consecutively enrolled and followed for 36 months after discharge. Serum CRP, NT-proBNP, and troponin T levels were determined. Right ventricular function was evaluated by transthoracic echocardiography.

Results

Right ventricular dysfunction was present in 31 patients and was more frequent in patients with higher CRP and NT-proBNP levels ( P = 0.020 and P = 0.045, respectively). During the 36-month follow-up, there were 15 terminal events (death due to recurrent PE). The mortality rate was 41.2% in patients with NT-proBNP levels greater than 1000 pg/mL, whereas it was 5.9% in patients with less than 500 pg/mL ( P = 0.011). Mortality rates also were higher in patients with elevated CRP and troponin T levels, but the differences did not reach clinical significance. The survival rate of acute PE patients with lower NT-proBNP and CRP levels was better than that of patients with higher NT-proBNP and CRP levels. Receiver operating characteristic curve analysis demonstrated cutoff values for NT-proBNP as 1800 pg/mL (sensitivity, 93.3%; specificity, 68.2%; positive predictive values, 66.7%; and negative predictive values, 93.8%) and for CRP as 48mg/L (sensitivity, 72.7%; specificity, 61.9%; positive predictive values, 50.0%; and negative predictive values, 81.3%) to predict mortality in PE patients.

Conclusions

C-reactive protein is associated with right ventricular dysfunction, which is a predictor of prognosis in PE and may become a promising biomarker for risk stratification of PE, although CRP is not found superior to NT-proBNP.
Interleukin 6 Promoter Polymorphisms in Normal Han Chinese Population: Frequencies and Effects on Inflammatory Markers
Authors: Pan Min , Gao Shu-Ping , Jiang Min-Hui , Guo Jing , Zheng Jin-Guo , Zhu Jian-Hua
Published: May 2016

Background

Interleukin 6 (IL-6) is a cytokine involved in different physiologic and pathophysiologic processes, and circulating levels of IL-6 differ greatly between individuals, but the results have not always been concordant among diverse populations. The aim of present study was to determine the prevalence of the 3 polymorphisms (−174G/C, −597G/A, and −634C/G) in the IL-6 gene promoter region and their effects on inflammatory markers in normal Han Chinese population.

Methods

A total of 232 subjects (143 men and 89 women; mean age, 51.37 ± 17.63 years; range, 22-88 years) of unrelated healthy Han Chinese in Jinangsu area (south of China) were enrolled. Genotyping of the 3 polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis and then confirmed by direct sequencing.

Results

Among the 232 individuals studied, 231 carried the GG wild type of -174G/C; only 1 carried the GC genotype. For -597G/A polymorphism, individuals all carried the GG wild type; the GA or AA genotypes were not detected. The frequencies of -634C/G genotypes CC, CG, and GG were found to be 59.48%, 37.07%, and 3.45%, respectively, the derived allele frequencies for the C and G alleles were 78.02% and 21.98%. There were no significant differences in age, sex, body mass index, or lipids parameters between the -634 CC and CG+GG genotypes. However, individuals with CC genotype showed lower levels of high-sensitivity C-reactive protein and IL-6 than those with CG+GG genotype.

Conclusions

IL-6 -174G/C and -597G/A are rare, but -634C/G is common in Han Chinese population, and the -634G allele is associated with circulating levels of IL-6 and C-reactive protein.
Early Erythropoietin Therapy Attenuates Remodeling and Preserves Function of Left Ventricle in Porcine Myocardial Infarction
Authors: Chua Sarah , Leu Steve , Lin Yu-Chun , Sheu Jiunn-Jye , Sun Cheuk-Kwan , Chung Sheng-Ying , Chai Han-Tan , Lee Fan-Yen , Kao Ying-Hsien , Wu Chiung-Jen , Chang Li-Teh , Ko Sheung-Fat , Yip Hon-Kan
Published: May 2016

Erythropoietin (EPO) has been shown to have anti-inflammatory, antiapoptotic, and proangiogenic effects. This study investigated whether early EPO treatment effectively preserves left ventricular (LV) function in porcine acute myocardial infarction (AMI). Eighteen male mini-pigs divided into groups 1 (sham), 2 (AMI), and 3 (AMI with 2 consecutive EPO doses [7500 IU per animal each time] at 30 minutes and 24 hours after AMI induction) underwent echocardiography before and 14 days after AMI induction through left anterior descending artery (LAD) ligation with myocardium harvested for analysis. Larger infarcted areas (IA) were noted in group 2 than in group 3. In both IA and peri-IA, percentage of apoptotic nuclei and CD40-positive cells, messenger RNA expressions of IL-8, matrix metalloproteinase-9, caspase-3, and Bcl-2 associated x protein were highest, whereas proliferator-activated receptor-γ coactivator-1α, endothelial nitric oxide synthase and Bcl-2 were lowest in group 2. Oxidative stress and cytosolic cytochrome c in IA were increased ( P < 0.001), whereas protein expression of connexin43, cytochrome c, and protein kinase C-ε in mitochondria were reduced in group 2 than in other groups ( P < 0.045). The fibrosis in IA was notably decreased in group 3 compared with that in group 2. The number of small arterioles and capillary density in IA was highest in group 3, whereas LV performance was lowest in group 2 ( P < 0.045). In conclusion, the results demonstrated that early EPO administration in a porcine AMI model effectively limits infarct size, attenuates LV remodeling, and preserves LV function.
Potential of Electron Beam Computed Tomography for Coronary Artery Calcium Screening to Evaluate Fatty Liver: Comparison with 1H Magnetic Resonance Spectroscopy in the Dallas Heart Study
Authors: Matulevicius Susan , Huff Laura C. , Szczepaniak Lidia S. , Ayers Colby R. , Budoff Matthew , McColl Roderick , Khera Amit , Peshock Ronald M.
Published: May 2016

Objectives

Electron beam computed tomography (EBCT) for coronary artery calcification can potentially evaluate liver fat, another marker of cardiovascular risk. We compared quantitative estimates of hepatic steatosis measured by EBCT with those obtained by a well-validated, accurate-measure, magnetic resonance spectroscopy (1H MRS).

Methods

EBCT and 1H MRS were performed in 2159 subjects from the Dallas Heart Study. Forty subjects were randomly selected from each of 5 subgroups of liver fat percent by 1H MRS (n = 200). EBCT average liver attenuation (HU) was determined in a 1- to 2-cm circular region of interest over the liver lobes. Pearson correlation coefficients were calculated. Using a previously defined 1H MRS hepatic steatosis cut point (>5.5%), an optimized EBCT liver attenuation cut point was determined by receiver operating characteristic analysis.

Results

1H MRS liver fat content and EBCT average right lobe liver attenuation were moderately negatively correlated ( r = −0.64, P < 0.0001) in all subjects and in those with 1H MRS hepatic steatosis ( r = −0.71, P < 0.0001). This correlation did not improve with attenuation correction of the EBCT data using a standard calcium phantom or statistical transformation. Using an optimized receiver operating characteristic EBCT cut point (64.5 HU), sensitivity was 78% and specificity was 72% for detecting 1H MRS hepatic steatosis, with a high false negative rate. Risk factors for hepatic steatosis (obesity, diabetes mellitus, insulin resistance, metabolic syndrome) were more strongly correlated with 1H MRS than EBCT liver fat measures.

Conclusions

Liver attenuation on EBCT acquired for coronary artery calcification screening correlates modestly with 1H MRS measures of liver fat content, with a high false negative rate.
Recent Insights into the Relationship between Inflammatory Liver Diseases and Atherosclerosis
Authors: Purnak Tugrul , Efe Cumali , Beyazit Yavuz , Ozaslan Ersan , Astan Ramazan , Milanlıoglu Aysel , Ozbalkan Zeynep , Rizzo Manfredi
Published: May 2016

Atherosclerosis is a dynamic process in the human body. Many studies have evaluated atherosclerosis and its relationship with other systems in the body. Our perception of its pathogenesis is evolving with the introduction of new players in the game. It is no longer possible to consider the atherosclerosis as an independent process, unaffected by the liver and its function. Although several tasks performed by the liver, such as lipid metabolism, have been implicated in the pathogenesis of atherosclerosis, the role of other disorders of the liver (autoimmune diseases, viral hepatitis, and cirrhosis) are not fully understood. In this review, the most commonly encountered inflammatory liver diseases and their effects on atherosclerosis are discussed.
Cardiac Resynchronization Therapy: Prospect for Long-Lasting Heart Failure Remission
Authors: Sun Shinning , Joglar Jose A.
Published: May 2016

Heart failure (HF) remains an important heath care problem in the United States. With the aging of the US population, this trend is expected to continue. However, patients have also benefited from advances in pharmacologic and device-based therapies such as angiotensin-converting enzyme inhibitors, β-blockers, aldosterone blockers, and implantable cardioverter-defibrillators. More recently, cardiac resynchronization therapy (CRT) has become another important therapeutic option for treating heart failure due to systolic dysfunction. In this article, we review the physiologic basis for CRT, the clinical trials that support its efficacy, and the current indications for its use. We also examine key clinical questions regarding CRT still under research, including predictors of response. Finally, we look at the future of CRT and how its indications can be expanded to benefit more patients in the future.
Computational Approaches for Translational Clinical Research in Disease Progression
Authors: McGuire Mary F. , Iyengar Madurai Sriram , Mercer David W.
Published: May 2016

Today, there is an ever-increasing amount of biological and clinical data available that could be used to enhance a systems-based understanding of disease progression through innovative computational analysis. In this article, we review a selection of published research regarding computational methods, primarily from systems biology, which support translational research from the molecular level to the bedside, with a focus on applications in trauma and critical care. Trauma is the leading cause of mortality in Americans younger than 45 years, and its rapid progression offers both opportunities and challenges for computational analysis of trends in molecular patterns associated with outcomes and therapeutic interventions.

This review presents methods and domain-specific examples that may inspire the development of new algorithms and computational methods that use both molecular and clinical data for diagnosis, prognosis, and therapy in disease progression.
Differential Association of Cytochrome P450 3A4 Genotypes with Onsets of Breast Tumors in African American versus Caucasian Patients
Authors: McDaniel D. Olga , Thurber Tonya , Lewis-Traylor Angela , Berry Crystal , Barber William Henry , Zhou Xinchun , Bigler Steven , Vance Ralph
Published: May 2016

Introduction

Malignant breast tumors are often hormone-dependent, and to this end, both estrogen and progesterone receptors are good prognostic markers for evaluation of the outcomes after therapy. In addition, HER-2/neu, whose expression is increasingly being associated with poor prognosis of breast cancer, has predictive potential after immunotherapy. Cytochrome P450 3A4 is highly involved in the metabolism of steroids. Thus, we investigated the impact of CYP 3A4 gene variants in association with clinical outcomes in African American (AFAM) versus Caucasian (CAU) patients with breast cancer diagnosis.

Methods

Patients who had undergone biopsy procedures for diagnosis or for partial or radical mastectomy were recruited. The CYP 3A4 genotypes (A or G) were detected using polymerase chain reaction amplification and primers designed for a single nucleotide polymorphism. The messenger RNA (mRNA) transcripts were screened by reverse transcription-polymerase chain reaction. Clinical data including tumor staging, pathology grades, and family history were evaluated.

Results

Frequency of the CYP 3A4-G (mutated variant) was significantly increased in AFAM patients as compared with controls ( P < 0.001). No statistically significant difference was observed between the genotypes comparing the benign versus ductal carcinomas in situ (DCIS) or infiltrating ductal carcinomas (IDCAs). In AFAM patients, GG alleles were increased in IDCA with stage III tumors, and in CAU patients, the AA alleles were increased with stage III tumors. The mRNA expression was reduced in patients with IDCA versus DCIS or benign tumors (benign vs IDCA, P < 0.0009; DCIS vs IDCA, P < 0.005), as well in HER-2/neu-positive tumors versus samples negative for receptors ( P < 0.0024).

Conclusions

Genotype association was affected by race. Expression levels of total CYP 3A4 mRNA were inversely correlated with clinical diagnosis. This may suggest mRNA testing as an additional tool that accelerates improvement in the diagnosis of the onsets of breast cancer.
Melanoma Antigen Encoding Gene-A3 Expression, Its Clinical Significance, and Its Risk of Developing Acute Myeloid Leukemia
Authors: Makhlouf Manal Mohamed
Published: May 2016

Background

Melanoma antigen encoding gene A3 (MAGE-A3) gene, also called cancer/testis (CT) antigen, is a member of MAGE multigene family, which is located on the long arm of the X chromosome, and its expression can be caused by promoter region demethylation. The MAGE-A3 proteins’ functions are unknown, but they were found to play a role in cell cycle progression, transcriptional regulation, and drug resistance. The aims of this study were to determine the expression of the MAGE-A3 gene in an Egyptian cohort of de novo acute myeloid leukemia (AML) patients and to define its role in the development of AML and its correlation with clinical presentation, laboratory data, as well as treatment outcome.

Patients and Methods

This study included 40 de novo AML patients as well as 30 age- and sex-matched normal healthy subjects as a control group. They were all subjected to reverse transcription-polymerase chain reaction assay for the detection of MAGE-A3 gene expression.

Results

Our study revealed that 23 AML patients (57.5%) expressed the MAGE-A3 gene, whereas none of the control group subjects (0%) expressed this gene. It was found that the expression of MAGE-A3 gene was associated with an increased risk of AML (odds ratio = 2.763; 95% confidence interval, 1.890-8.041). Regarding treatment outcome, a highly statistical significant difference was found between MAGE-A3-positive and -negative AML patients with P < 0.001, as the MAGE-A3-positive AML patients had a higher incidence of unfavorable treatment outcome, whereas the MAGE-A3-negative patients had a higher incidence of favorable outcome. This clarifies that the MAGE-A3 gene expression was found to have a significant impact on the risk of treatment failure (odds ratio = 3.591; 95% confidence interval, 1.273-10.462).

Conclusions

The expression of MAGE-A3 gene may have a clinical relevance and important role as a risk factor in the development of AML. It may be considered as a prognostic marker and may be useful as a predictive test for treatment outcome in AML.
Association between Serum Vitamin B12 Levels and the Degree of Steatosis in Patients with Nonalcoholic Fatty Liver Disease
Authors: Koplay Mustafa , Gulcan Erim , Ozkan Fuat
Published: May 2016

Purpose

A relationship between liver diseases and serum vitamin B12 levels was observed in previous reports. The purpose of this study was to determine if a similar relationship existed between vitamin B12 and nonalcoholic fatty liver disease (NAFLD), a common chronic liver disorder.

Materials and Methods

A total of 45 consecutive patients with NAFLD formed the NAFLD group, whereas 30 healthy controls (HC) formed the HC group. The subjects in all of the groups were of similar age and body mass index (BMI). A fatty liver is described in 3 ultrasonographic grades. Fasting blood samples were obtained, and serum vitamin B12 levels were measured. In addition, liver enzymes including aspartate aminotransferase, alanine aminotransferase (ALT), and alkaline phosphatase, and folic acid and other serum parameters were evaluated. The Mann-Whitney U test, χ2 test, and Spearman correlation analysis were used to compare the vitamin B12 levels and other serum parameters in both groups.

Results

The mean ± SD age and BMI of the NAFLD were 47.2 ± 11.2 and 28.8 ± 3.5. The mean ± SD age and BMI of the HC were 47.1 ± 8.8 and 27.7 ± 2.9, respectively. The serum aspartate aminotransferase and ALT levels of the patients with NAFLD were statistically higher compared with those of the controls ( P = 0.001). The levels of vitamin B12 and folate were statistically lower in the NAFLD patients compared with those of the controls ( P < 0.05). We found that there was a reduction of vitamin B12 levels, especially in grade 2 to grade 3 hepatosteatosis. In addition, in the Spearman correlation analysis between the vitamin B12 levels and ALT, the grade of fatty liver and the liver dimension were found to have an important negative correlation.

Conclusion

The serum vitamin B12 levels were significantly lower in the patients with NAFLD than in those of the control group; however, these still remain in the reference range. Consequently, low vitamin B12 levels may be associated with NAFLD especially in grade 2 to grade 3 hepatosteatosis.
Effective Out-of-Operating Room Airway Management for Physicians Not Traditionally Trained in Airway Management
Authors: Kessler Chad S. , Tristano Jenny M. , Dignan Mary Ann , Xie Hui , Stallings Leonard A. , Albrecht Ronald F.
Published: May 2016

Background

There is a dearth of literature about the safety and practicality of intubation performed by an internal medicine (IM) or any other nonanesthesia, nonemergency physician.

Objectives

The objectives of the study were to describe abbreviated airway management training guidelines for IM physicians staffing the emergency department and to compare the success rates between intubations performed by anesthesia and IM physicians, respectively.

Methods

In this study, 272 consecutive out-of-operating room intubations performed by anesthesia and IM physicians were evaluated after creating and implementing an abbreviated intubation training protocol.

Results

Of 165 intubations attempted by IM physicians and 107 intubations attempted by the anesthesia service, the rates of successful intubation were 93% and 99%, respectively ( P = 0.02). There were no other statistically significant differences in outcomes.

Conclusions

Procedurally oriented IM fellows could provide a temporary solution to hospitals that currently do not have the resources to provide full-time, in-house anesthesiology or emergency physicians for management of the emergent airway.
The Evaluation of Hypoxia-Inducible Factor 1 in N-Nitro-L-Arginine Methyl Ester Preeclampsia Model of Pregnant Rats
Authors: Kaya Ali , Boztosun Abdullah , Seckin Hulya , Guven Ahmet Sami , Kucukdurmaz Zekeriya , Gulturk Sefa , Cevit Omer
Published: May 2016

Objective

The objective of the study was to evaluate hypoxia-inducible factor 1 (HIF-1), which plays a major role in the stimulation of angiogenesis in placental tissues, by using immunohistochemical staining in preeclampsia model of rats, developed by N-nitro-L-arginine methyl ester (L-NAME)

Methods

Thirty pregnant rats were randomized into 2 groups (n = 15 in each group) on day 10 of gestation. L-NAME was given to rats in the study group by gavage. On days 0, 10, and 20 of gestation, rats were weighted, and urine protein values and blood pressures were measured. Hypoxia-inducible factor 1 expressions were assessed with immunohistochemical staining by using avidin-biotin peroxidase via selecting preparation.

Results

Systolic and diastolic blood pressures and urine protein value of L-NAME group on day 20 of gestation were found to be significantly higher than those obtained on days 0 and 10 of gestation in the same group and those obtained on day 20 of gestation in the sham group ( P < 0.05). Maternal weight, number of fetuses, and mean fetal weight of rats in L-NAME group on day 20 of gestation were found to be significantly lower than those obtained from rats in the sham group ( P < 0.05). Regarding HIF-1 expression of placental tissues, mild immunohistochemical staining was found in 2 rats (13.4%) and moderate in 13 rats (86.6%) in the L-NAME group. A significant difference was found in terms of HIF-1 positivity in the maternal placentas of both groups ( P < 0.05).

Conclusions

L-NAME preeclampsia model of pregnant rats is consistent with human preeclampsia in terms of hypertension, proteinuria, and intrauterine growth retardation; in addition, it also shows evidence of placental hypoxia findings.
Mechanism of Action of Vitamin D in the Asthmatic Lung
Authors: Iqbal Sabah Fatima , Freishtat Robert J.
Published: May 2016

Vitamin D, or 1,25-dihydroxy vitamin D (1,25[OH]D), in its activated form, has long been recognized as a critical mediator in bone health. New research has identified 1,25(OH)D as also vital for respiratory health. Owing to its intrinsic anti-inflammatory properties, 1,25(OH)D may be very important in people with asthma. This review article seeks to evaluate the current literature to delineate the potential mechanisms of action by which 1,25(OH)D affects asthma. We summarize the evidence that 1,25(OH)D has receptors in multiple lung cell types and acts to abrogate asthma by several mechanisms: promoting lung immunity, decreasing inflammation, slowing cell cycling, reducing hyperplasia, and enhancing the effects of exogenous steroids. Put together, there is compelling evidence for the role of vitamin D in asthma.
Conductive Energy Devices: A Review of Use and Deaths in the United States
Authors: Nugent Kenneth , Bagdure Satish , Otahbachi Mohammad , Cevik Cihan
Published: May 2016

Background

Conductive energy devices (CEDs) have been temporally associated with morbidity and mortality in police work, but the frequency of use and of complications is not certain.

Methods

This is a literature review using PubMed and Google Scholar searches to identify population-based CED studies, studies reporting morbidity and mortality with CEDs, and studies in healthy volunteers.

Results

Recent studies indicate that CEDs are used approximately 83 to 338 times per million population per year in the United States. The subjects have a typical profile, including young men with belligerent or bizarre behavior who often have a psychiatric disorder or are intoxicated with drugs. The mortality estimates range from 0.0% to 1.4% of subjects controlled with CEDs. Limited information from autopsy studies indicates that death is frequently associated with confounding factors, especially intoxication with illicit drugs.

Conclusions

Conductive energy devices are used frequently during police work and are associated with a low but definite mortality rate. The use of CEDs and the management of at-risk subjects need more study.
High Rates of Intestinal Colonization with Extended-Spectrum Lactamase-Producing Enterobacteriaceae among Healthy Individuals
Authors: Abdul Rahman Eiman Mohammed , El-Sherif Rasha Hamed
Published: May 2016

Background

Infections caused by extended-spectrum β-lactamase (ESBL)-producing bacteria become an emerging problem in the community setting in many parts of the world.

Objective

The objective of the study was to determine fecal carriage of ESBL-producing organisms in a community setting.

Methods

A total of 632 fecal specimens from healthy individuals were screened for ESBL using the agar screening test with MacConkey agar plates supplemented with 1 μg/mL of cefotaxime for selection of ESBL-producing strains and confirmed by the Clinical Laboratory Standards Institute combined disk method.

Results

Four hundred isolates (63.3%) were ESBL producers. Two hundred eighty-five isolates (71.25%) of them were Escherichia coli and 96 (24.0%) Klebsiella pneumoniae.

Conclusion

We concluded that the community could be a reservoir of these ESBL-producing bacteria and enzymes.
Clostridium difficile Infection is Associated with Poor Outcomes in End-Stage Renal Disease
Authors: Pant Chaitanya , Deshpande Abhishek , Anderson Michael P. , Sferra Thomas J.
Published: May 2016

Objective

To investigate the association of Clostridium difficile infection (CDI) with the outcomes of hospitalized patients with end-stage renal disease (ESRD).

Methods

We extracted all adult cases with a discharge diagnosis of ESRD or CDI from the United States Nationwide Inpatient Sample 2009 database. Outcome variables (mortality, length of hospital stay [LOS], and hospitalization charges), demographic information, and comorbidity data were collected. Data were evaluated by univariate and multiple regression analyses.

Results

We identified 184,139 cases with ESRD of which 2.8% had CDI. Comparison of patients with ESRD + CDI to those with only ESRD revealed in-hospital mortality (13.2% vs 5.3%; P < 0.001), LOS (17.3 vs 7.1 days; P < 0.001), and charges ($124,846 vs $56,663; P < 0.001) to be more than 2-fold greater. In the ESRD cohort (ESRD only and ESRD + CDI), CDI was independently associated with greater mortality (adjusted odds ratio, 2.15; 95% CI, 2.07–2.24; P < 0.001), longer LOS (mean difference, 9.4 days; 95% CI, 9.2–9.5; P < 0.001), and higher charges (mean difference, $62,824; 95% CI, 61,615–64,033; P < 0.001).

Conclusions

Clostridium difficile infection is associated with significantly worse outcomes in hospitalized patients with ESRD.
Association of Genetic Polymorphisms in the Paraoxonase 1 Gene with the Risk and Prognosis of Non–Small Cell Lung Cancer in Chinese Han Population
Authors: Wang Hui , Li Lin , Ding Li , Zhang Zijin , Pu Chun
Published: May 2016

Objective

Oxidative stress and free radicals have been indicated to be associated with increased risk of various cancers. Paraoxonase 1 ( PON1) gene, encoding PON1 protein, plays an important role as an endogenous free-radical scavenging molecule. The aim of the present study was to determine whether genetic polymorphisms of the PON1 gene are associated with the risk and prognosis of non–small cell lung cancer (NSCLC).

Methods

A total of 356 patients with NSCLC and 184 healthy controls were enrolled in this study. Q192R and L55M polymorphisms of the PON1 gene were genotyped using polymerase chain reaction and restriction fragment length polymorphism method.

Results

As for the Q192R polymorphism, the patients with NSCLC showed higher frequencies of QR and RR genotypes than the normal controls. Unconditional logistic regression analysis revealed that QR and RR genotypes were significantly associated with the presence of NSCLC compared with the QQ genotype. No significant differences were found in the genotypes of the L55M polymorphism between the patients with NSCLC and the healthy controls. The QR and RR genotypes were significantly associated with TNM stage and nodal metastasis. Survival analysis indicated that the patients with NSCLC with the QR and RR genotypes had poorer disease-free survival than those with the QQ genotype ( P = 0.011). Multivariable Cox regression analysis revealed that QR and RR genotypes were an independent factor for the prognosis of NSCLC (hazard ratio, 1.505; 95% confidence interval, 1.004–2.256; P = 0.048).

Conclusion

The Q192R polymorphism of the PON1 gene may be associated with the risk and prognosis of NSCLC in a Chinese Han population.
Tools for Productively Managing Conflict
Authors: Zucker Deborah
Published: May 2016

In scientific teams as in life, conflicts arise. This paper aims to provide an introduction to tools and skills to help in managing conflicts in practice. Using a structured approach enables the concerns and interests of all involved to be identified and clarified. It also permits a better understanding of yourself and others and will help empower those in conflict to find acceptable and workable resolutions.
Serum Levels of Angiopoietin-Related Growth Factor (AGF) are Increased in Polycystic Ovary Syndrome
Authors: Boztosun Abdullah , Deveci Köksal , Kiliçli Fatih , Söylemez Melike Sinem , Muhtaroğlu Sabahaddin , Müderris İptisam İpek
Published: May 2016

Background

Polycystic ovary syndrome (PCOS) is a frequent reproductive and metabolic disorder associated with insulin resistance. Recently, angiopoietins were identified in the systemic circulation and have been designated angiopoietinlike proteins (ANGPTL). More recently, it is shown that angiopoietin-related growth factor (AGF, also called ANGPTL6) directly regulate lipid, glucose, and energy metabolism independent of angiogenic effects in animal studies. The aim of this study was to determine whether there is an association between AGF and PCOS.

Methods

The study included 35 patients with PCOS and 30 healthy control women. We analyzed serum levels of AGF and other biochemical and anthropometric markers in all the subjects.

Results

This study showed that serum AGF levels were significantly higher in the subjects with PCOS (102.28 ng/mL) than those in the healthy control group (63.08 ng/mL; P < 0.001). Body mass index (24.33 vs 22.11 kg/m2; P = 0.017), free testosterone (2.81 vs 2.17 pmol/L; P = 0.009), androstenedione (3.28 vs 2.92 nmol/L; P = 0.033), 17-hydroxyprogesterone (2.72 vs 2.09 ng/mL; P = 0.039), homeostasis model of assessment-insulin resistance (2.65 vs 1.9; P = 0.016), and fasting glucose (107.09 vs 96.18 mmol/L; P = 0.001) were found significantly higher in PCOS group than in control group. But there was no correlation between AGF and these parameters in PCOS group. In addition, no correlation between the AGF and other distinctive features of PCOS was found.

Conclusions

Serum AGF levels were paradoxically increased in patients with PCOS in comparison with data of animal experiments. Further studies are needed to better elucidate the physiologic significance of circulating AGF in human disease.
Serum Cytokines and Cancer in Involuntary Weight Loss
Authors: Baicus Cristian , Caraiola Simona , Rimbas Mihai , Patrascu Ruxandra , Baicus Anda
Published: May 2016

Background

Tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 may be associated with involuntary weight loss in patients with and without cancer. However, results of previous studies have been conflicting. We evaluated patients who had involuntary weight loss to determine cytokine levels and the correlation of these cytokines with weight loss, the association with inflammation, and the potential for use in cancer diagnosis.

Materials and Methods

In 290 consecutive patients with involuntary weight loss (74 patients [26%] with cancer and 216 patients [74%] without cancer), erythrocyte sedimentation rate (ESR), and serum levels of C-reactive protein, TNF-α, IL-1β, and IL-6 were determined.

Results

Higher ESR and levels of C-reactive protein, TNF-α, IL-1β, and IL-6 were associated with cancer. The levels of TNF-α, IL-1β, and IL-6 did not correlate with the amount of weight loss. In multivariable analysis, only ESR was associated with cancer.

Conclusions

In patients with involuntary weight loss, TNF-α, IL-1β, and IL-6 were associated with cancer but were not weight loss mediators.
Genetic Influences on Vitamin D Status and Forearm Fracture Risk in African American Children
Authors: Ryan Leticia Manning , Chamberlain James M. , Singer Steven A. , Wood Rachel , Tosi Laura L. , Freishtat Robert J. , Gordish-Dressman Heather , Teach Stephen J. , Devaney Joseph M.
Published: May 2016

We sought to investigate the relationship between newly identified genetic variants and vitamin D levels and fracture risk in healthy African American (black) children. This case-control study included children of both sexes, ages 5 to 9 years, with and without forearm fractures. Serum 25-hydroxy vitamin D levels, bone mineral density, body mass index, and calcium/vitamin D intake were measured in 130 individuals (n = 60 cases and n = 70 controls). The 5 variants tested were located in the GC gene (rs2282679), in the NADSYN1 gene (rs12785878 and rs3829251), and in the promoter region of the CYP2R1 gene (rs2060793 and rs104741657). Associations between single nucleotide polymorphisms (SNPs) and vitamin D levels were tested using an analysis of covariance. Associations between SNPs and fracture status were tested using logistic regression. The GC gene variant was associated with vitamin D levels ( P = 0.038). None of the SNPs were associated with fracture status in young blacks. These results suggest that the variants tested, which are associated with circulating vitamin D levels in whites, are not associated with fracture status in healthy black children. Additional research is required to discover the genetics of fracture risk in blacks.
Effect of Insulin versus Triple Oral Therapy on the Progression of Hepatic Steatosis in Type 2 Diabetes
Authors: Lingvay Ildiko , Roe Erin D. , Duong Jonathan , Leonard David , Szczepaniak Lidia S.
Published: May 2016

Background

Hyperinsulinemia has been associated with hepatic fat deposition and ensuing insulin resistance. It is unknown if treatment with exogenous insulin in patients with type 2 diabetes, who are most prone to hepatic fat accumulation, would promote the occurrence or worsening of nonalcoholic fatty liver disease.

Methods

Patients with treatment-naive type 2 diabetes (N = 16) were treated with insulin and metformin for a 3-month lead-in period, then assigned triple oral therapy (metformin, glyburide, and pioglitazone) or continued treatment with insulin and metformin. Hepatic triglyceride content (HTC)—measured by magnetic resonance spectroscopy, serum lipids, glucose, liver function tests, and inflammatory and thrombotic biomarkers were followed for a median of 31 months.

Results

The 45% decline in HTC during the lead-in period persisted through the follow-up period with no difference between treatment groups at the end of the study (5.26 ± 4.21% in the triple oral therapy vs 7.47 ± 7.40% for insulin/metformin), whereas glycemic control was comparable.

Conclusions

Improvements in HTC with initial insulin/metformin therapy persisted through the median 31-month follow-up period regardless of the treatment. More importantly, insulin-based treatment did not appear to promote or worsen nonalcoholic fatty liver disease.
Understanding Food and Drug Administration Regulatory Requirements for an Investigational Device Exemption for Sponsor-Investigators
Authors: Holbein M. E. Blair , Berglund Jelena Petrovic
Published: May 2016

Clinical investigators in academic medical centers often perceive federal regulations as a significant obstacle to conducting clinical research. The regulatory authority of the Food and Drug Administration (FDA) extends to clinical studies of medical devices. Consequently, researchers wishing to conduct device research using FDA-approved as well as nonapproved devices must comply with federal regulations for investigational device exemptions (IDE) as described in Title 21 of the Code of Federal Regulations Part 812. FDA regulatory oversight is structured to match the risk to the subject to the risk of the device. Medical device studies can be categorized as follows: meeting exemption criteria, being a nonsignificant risk device, or being a significant risk device. All IDE studies must meet regulations for the protection of human subjects, but no additional federal filing on the part of the investigator is necessary for those that meet exempt criteria. Nonsignificant risk device studies require meeting abbreviated IDE regulatory requirements for the conduct of the study, but no previous FDA approval is required. Significant risk device studies require that the investigator also function as a sponsor and to file an IDE with the FDA for approval before starting. A sponsor-investigator filing an IDE follows the format and content described in 21 CFR 812.20. The study may begin 30 days after the date of submission receipt unless the FDA notifies the sponsor otherwise. While the IDE is active, the sponsor-investigator must meet the requirements for the conduct of the study and the required monitoring and reporting to the FDA.
MicroRNA-30b-5p is Involved in the Regulation of Cardiac Hypertrophy by Targeting CaMKIIδ
Authors: He Juan , Jiang Shan , Li Feng-lan , Zhao Xue-jiao , Chu Er-fu , Sun Mei-na , Chen Ming-zi , Li Hui
Published: May 2016

Background

MicroRNAs (miRNAs) participate in the regulation of cardiac hypertrophy. However, it remains largely unknown as to how miRNAs are integrated into the hypertrophic program. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a hypertrophic signaling marker. It is not yet clear which miRNAs can regulate CaMKIIδ.

Purpose

In this study, we identified which miRNAs could regulate CaMKIIδ and how to regulate CaMKIIδ.

Methods

Through computational and expression analyses, miR-30b-5p was identified as a candidate regulator of CaMKIIδ. Quantitative expression analysis of hypertrophic models demonstrated significant down-regulation of miR-30b-5p compared with control groups. Luciferase reporter assay showed that miR-30b-5p could significantly inhibit the expression of CaMKIIδ. Moreover, through gain-of-function and loss-of-function approaches, we found miR-30b-5p could negatively regulate the expression of CaMKIIδ and miR-30b-5p was a regulator of cardiac hypertrophy.

Conclusion

Our study demonstrates that the expression of miR-30b-5p is down-regulated in cardiac hypertrophy, and restoration of its function inhibits the expression of CaMKIIδ, suggesting that miR-30b-5p may act as a hypertrophic suppressor.
Fasting Glucose Level Modulates Cell Surface Expression of CD11b and CD66b in Granulocytes and Monocytes of Patients with Type 2 Diabetes
Authors: Horvath Peter , Oliver Stacy R. , Ganesan Goutham , Zaldivar Frank P. , Radom-Aizik Shlomit , Galassetti Pietro R.
Published: May 2016

Introduction

Cardiovascular complications are the leading cause of mortality in type 2 diabetes (T2DM), in which onset and progression of atherosclerosis is linked to chronic inflammation. Activation status of innate immune cells (granulocytes [Gc], monocytes [Mc]), as reflected by increased CD11b, CD66b, and other surface markers, increases their endothelial and cytokines/chemokines release. Whereas this inflammatory activation seems inversely related to poor glycemic control, the effect of acute spontaneous hyperglycemia on innate immune cell activation remains unclear.

Methods

Expression of key markers (CD11b, CD14, CD16, CD62L, and CD66b) was therefore determined by flow cytometry on whole blood of healthy subjects and patients with T2DM with spontaneous fasting euglycemia or hyperglycemia both at baseline and after 30, 90, and 240 minutes of incubation at room temperature.

Results

Hyperglycemic patients with T2DM had significantly higher Gc and Mc CD11b and Gc CD66b surface mean fluorescence intensity compared with the euglycemic patients with T2DM whose values were similar to those of the healthy controls. CD16 expression in CD14+CD16+ Mc was elevated in all patients with T2DM, regardless of glycemic levels.

Conclusion

Our data suggest that whereas the presence of diabetes per se may have a proinflammatory effect, hyperglycemia seems to further acutely exacerbate innate cell inflammatory status and their consequent endothelial adhesion and vascular damage potential.