bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between Genetic Variants in Vitamin D Metabolism and Asthma Characteristics in Young African Americans: A Pilot Study
Authors: Pillai Dinesh K. , Iqbal Sabah F. , Benton Angela S. , Lerner Jennifer , Wiles Andrew , Foerster Matthew , Ozedirne Tugba , Holbrook Henry P. , Payne Perry W. , Gordish-Dressman Heather , Teach Stephen J. , Freishtat Robert J.
Published: May 2016

Introduction

Low vitamin D levels have been associated with asthma severity in children. Young, urban African Americans (AAs) have high rates of hypovitaminosis D and asthma. Our objective was to determine associations between variants in vitamin D metabolism genes and asthma characteristics in a pilot study of young urban AAs.

Materials and Methods

Two urban AA cohorts of subjects aged 6 to 20 years (139 subjects with asthma and 74 subjects without asthma) were genotyped for 12 single nucleotide polymorphisms (SNPs) in 3 vitamin D metabolism genes: VDR (vitamin D receptor), CYP24A1 (cytochrome P450 vitamin D 24-hydroxylase), and CYP2R1 (cytochrome P450 vitamin D 25-hydroxylase). In a case-control analysis, SNPs were studied for associations with an asthma diagnosis. Within the asthmatic cohort, SNPs were analyzed for associations with quantitative asthma characteristics. All analyses were adjusted for age, sex, and body mass index percentile.

Results

Only the CYP2R1 SNP rs10766197 homozygous minor genotype was associated with asthma ( P = 0.044). CYP24A1 SNP rs2248137 was associated with lower vitamin D levels ( P = 0.006). Within the asthma cohort, multiple significant associations between SNPs and asthma characteristics were identified; VDR SNP rs2228570 was associated with the higher nighttime asthma morbidity scores ( P = 0.04), lower baseline spirometric measures ( P < 0.05), 1 or more positive aeroallergen skin test ( P = 0.003), and increased immunoglobulin E levels ( P < 0.001).

Discussion

This pilot study demonstrates that variants in vitamin D metabolism genes are associated with quantitative asthma characteristics in young, urban AAs. The collection of these associations provides evidence for the need for a large population-based study of vitamin D-relevant SNPs in this cohort.
17β-Estradiol Inhibits Oxidized Low-Density Lipoprotein-Induced Increase in Matrix Metalloproteinase-9 Expression in Human Macrophages
Authors: Uzui Hiroyasu , Sinha Satyesh K. , Rajavashisth Tripathi B.
Published: May 2016

Beneficial effects of estrogen have been attributed to improved lipid profiles and to direct effects on the arterial wall. Macrophage-derived matrix metalloproteinases (MMPs) are expressed in atherosclerotic plaques, where they may contribute to plaque disruption. We have shown that oxidized low-density lipoprotein (Ox-LDL) increases matrix metalloproteinase-9 (MMP-9) expression in macrophages (Mφ). In this study, we tested the hypothesis that 17β-estradiol regulates basal and Ox-LDL-induced expression of MMPs and their tissue inhibitor (TIMPs) in human Mφ. Peripheral blood mononuclear cells isolated from normal human subjects were cultured for 7 days to transform into Mφ. On day 7, Mφ were starved with serum-free medium for 16 hours and then treated with 17β-estradiol and/or progesterone (PROG) in the presence or absence Ox-LDL for 24 hours. Levels and activity of MMP-2 and MMP-9 and levels of TIMP-1 and TIMP-2 were determined. After exposure to Ox-LDL, MMP-9 expression increased by 60% and TIMP-1 expression decreased by 29% ( P < 0.05 and P < 0.05, respectively, compared to control), whereas TIMP-2 expression was unchanged. 17β-estradiol reduced the levels of Ox-LDL-induced MMP-9 protein as measured by Western blot ( P < 0.05; n = 5) and Ox-LDL-induced MMP-9 activity ( P < 0.05; n = 5) as measured by gelatin zymography. Conclusively, estradiol abolished Ox-LDL-stimulated increase in the levels of macrophage-derived MMP-9 protein and activity in human Mφ. This effect was reversed by TAM but not by PROG. These data suggest that at least part of the protective effect of estrogen occurs by attenuation of Ox-LDL alterations in MMP-9 expression.
RAD51 and XRCC3 Gene Polymorphisms and the Risk of Developing Acute Myeloid Leukemia
Authors: Hamdy Mona S. , El-Haddad Alaa M. , Bahaa El-Din Neveen M. , Makhlouf Manal Mohamed , Abdel-Hamid Samah M.
Published: May 2016

RAD51 (Rec A homolog of E.coli) is a polymorphic gene and one of the central proteins in homologous recombination-DNA-double-stand breaks (HR-DNA-DSB) repair pathway, which is vital in maintaining genetic stability within a cell. The x-ray repair cross complementing (XRCC3) protein also functions in HR-DNA-DSB repair pathway and directly interacts with and stabilizes RAD51 and the closely related RAD51C. The aim of this study was to determine the prevalence of the RAD51 and XRCC3 repair gene polymorphisms among acute myeloid leukemia (AML) patients and to define their role in development of AML and its correlation with the clinical presentation, laboratory data as well as treatment outcome using polymerase chain reaction-restriction fragment length polymorphism assay in 50 de novo AML patients as well as 30 healthy subjects as a control group. Our study revealed that RAD51 G135C and XRCC3 Thr241Met alleles were associated with increased risk of AML with odds ratio (OR) of 2.833 and 2.909 and 95% confidence interval (CI) of 1.527 to 8.983 and 1.761 to 9.788, respectively. Moreover, when combining the 2 genes polymorphisms, a significant elevation of the risk of AML was found with OR of 3.124 and 95% CI of 1.872 to 11.243. As regards treatment outcome, a highly statistical significant difference was found between XRCC3 genotypes with P value of 0.001, whereas no significant difference was present between RAD51 genotypes with P value of 0.29. This clarifies that XRCC3 gene polymorphisms was found to have a significant impact on the risk of treatment failure with OR of 3.560 and 95% CI of 1.167 to 10.875; however, RAD51 gene polymorphism was not found to have an equivalent effect with OR of 2.813 and 95% CI of 0.933 to 10.828. So XRCC3 gene polymorphism might be considered as a prognostic marker in AML. In conclusion, RAD51 and XRCC3 genes polymorphisms may play an important role in the development of AML.
Body Fat Distribution and Its Association with Hypertension in a Sample of Mexican Children
Authors: Ramos-Arellano Luz Elena , Benito-Damián Fabián , Salgado-Goytia Lorenzo , Muñoz-Valle José Francisco , Guzmán-Guzmán Iris Paola , Vences-Velázquez Amalia , Castro-Alarcón Natividad , Parra-Rojas Isela
Published: May 2016

Background

The association between elevated blood pressure and childhood overweight and obesity has been documented in several studies. However, the linkage of blood pressure with body fat distribution in children is not well established. We investigated the relationship between both central and subcutaneous adiposity with BP in the 95th percentile or higher in Mexican children.

Methods and Results

Our study, using a sample of children from the State of Guerrero, Mexico was comprised of 252 children, 124 girls and 128 boys, with an age range of 6 to 13 years. Resting blood pressure was measured in duplicate with an aneroid sphygmomanometer. Hypertension was classified as systolic or diastolic BP in the 95th percentile or higher. Additional measures included weight, height, body mass index, body circumferences, and skinfold thickness. The prevalence of obesity (26.5%) was higher than overweight (15.8%), but the prevalence of hypertension was moderate (4.7%). Both systolic and diastolic blood pressures correlated strongly with age, weight, height, and all measurements of central and subcutaneous adiposity. Interestingly, after being adjusted by age, sex, and body mass index, the BP in the 95th percentile or higher was associated with suprailiac skinfold, third tertile (OR = 11.83, P = 0.023); triceps skinfold, third tertile (OR = 6.02; P = 0.034); and biceps skinfold, third tertile (OR = 4.71; P = 0.038).

Conclusions

Our data indicate that the prevalence of hypertension in children is moderate. In addition, the skinfold thickness was a better predictor of hypertension than central adiposity in the sample of children studied.
Suppressive Effects of Imidapril on Th1- and Th2-Related Chemokines in Monocytes
Authors: Tsai Ming-Kai , Jan Ren-Long , Lin Ching-Hsiung , Kuo Chang-Hung , Yang San-Nan , Chen Huan-Nan , Huang Ming-Yii , Hung Chih-Hsing
Published: May 2016

Background

Angiotensin-converting enzyme inhibitors (ACEIs) are used to control hypertension and are superior to other antihypertensive agents in protecting the progressive deterioration of autoimmune-related nephritis. An imbalance of T helper 1 (Th1)/Th2 is thought to contribute to the pathogenesis of autoimmune diseases and their related glomerulonephritis. I-309 is a Th2-related chemokine involved in the recruitment of Th2 cells toward Th2-related inflammation. Tumor necrosis factor α (TNF-α) and Th1-related chemokines, interferon-inducible protein 10 (IP-10)/CXCL10 are also involved in autoimmune glomerulonephritis. However, the modulatory effects and the mechanisms of ACEIs on TNF-α and Th1- and Th2-related chemokines in monocytes remain poorly defined.

Objective

We investigated the effects of imidapril and perindopril, 2 ACEIs, on the expression of IP-10, I-309, and TNF-α in human monocytes and also the associated intracellular mechanism.

Results

Imidapril and perindopril significantly downregulated lipopolysaccharide (LPS)-induced TNF-α, I-309, and IP-10 in THP-1 cells and human primary monocytes. All 3 mitogen-activated protein kinase inhibitors suppressed LPS-induced TNF-α and I-309 expression in human primary monocytes. Only extracellular signal-regulated kinases and c-Jun N-terminal kinases (JNK) mitogen-activated protein kinase inhibitors suppressed LPS-induced IP-10 expression. Lipopolysaccharide-induced mitogen-activated protein kinase kinase 4 (MKK4), p-JNK, and c-Jun expression in human primary monocytes was suppressed by imidapril.

Conclusions

These data demonstrate that ACEI is effective in downregulating LPS-induced TNF-α, I-309, and IP-10, which play important roles in the pathogenesis of inflammation. Its suppressive effect on TNF-α, I-309, and IP-10 may, at least in part, involve the down-regulation of LPS-induced MKK4-JNK-c-Jun expression.
P-Wave Duration and Dispersion in Patients with Emery-Dreifuss Muscular Dystrophy
Authors: Russo Vincenzo , Rago Anna , Palladino Alberto , Papa Andrea Antonio , Di Meo Federica , Della Cioppa Nadia , Golino Paolo , Russo Maria Giovanna , Calabrò Raffaele , Politano Luisa , Nigro Gerardo
Published: May 2016

Background

Paroxysmal episodes of atrial fibrillation frequently occur in Emery-Dreifuss muscular dystrophy (EDMD). Although previous studies have documented a variety of electrocardiographic abnormalities in EDMD, little is still known about P-wave dispersion (PD), an independent risk factor for the development of atrial fibrillation. The aim of our study was to evaluate the P-wave duration and PD in patients with EDMD with conserved systolic and diastolic cardiac function.

Methods

The study involved 36 patients with EDMD (age, 20 [SD, 12] years; 26 men) and 36 healthy subjects used as controls, matched for age and sex. P-wave dispersion was carefully measured using 12-lead electrocardiogram. Compared with the healthy control group, patients with EDMD presented increased maximum P-wave duration (108.2 [SD, 22.2] vs 97.8 [SD, 11] milliseconds, P = 0.04) and PD (51.4 [SD, 12.8] vs 39.3 [SD, 9.7] milliseconds, P = 0.004) values. No statistically significant differences in left atrium diameter (37.1 [SD, 2.9] vs 34.1 [SD, 4.2] mm, P = 0.3) and maximum left atrium volume (15.2 [SD, 3.8] vs 14.1 [SD, 4.2] mL/m2, P = 0.4) were found between the 2 groups. We divided our study population into 2 subgroups, according to the different genetic diagnosis, patients with laminopathy EDMD (n = 17) or with emerinopathy EDMD (n = 19). No statistically significant differences were found in PD between the 2 subgroups (54.6 [SD, 15.6] vs 50.2 [SD, 11.5] milliseconds, P = 0.4).

Conclusions

Our study showed a significant increase of maximum P-wave duration and PD in patients with EDMD with conserved systolic and diastolic cardiac function.
Acute Kidney Injury and Chronic Kidney Disease in Hospitalized Patients with Cirrhosis
Authors: Warner Nafisseh Sirjani , Cuthbert Jennifer A. , Bhore Rafia , Rockey Don C.
Published: May 2016

Background

Renal dysfunction is a common and potentially life-threatening complication in hospitalized patients with cirrhosis.

Aims

To determine the prevalence, cause, and outcome of patients with cirrhosis and acute kidney injury (AKI) and/or chronic kidney disease (CKD).

Methods

This retrospective analysis examined hospital records of 152 consecutive patients with cirrhosis and creatinine levels of 1.5 mg/dL or greater. Multiple clinical and laboratory variables were abstracted for each subject. Precise definitions were used to define cirrhosis and etiologies of renal dysfunction. Univariate and multivariable logistic regression analyses were performed to identify features with prognostic value for hospital mortality.

Results

The most common type of renal dysfunction was AKI, present in 107 patients (70%). Acute kidney injury plus CKD was found in 26 patients (17%), and CKD alone was present in 19 patients (13%). Prerenal azotemia was the most common cause of AKI (69%), often occurring secondary to gastrointestinal hemorrhage. The overall mortality for the cohort was 31%, with the highest mortality occurring in patients with type 1 hepatorenal syndrome (HRS) (11/14, 79%). We were unable to identify any patient meeting diagnostic criteria for type 2 HRS. The development of AKI on preexisting CKD did not infer worse prognosis than AKI alone. The presence of upper gastrointestinal bleeding, bacteremia, and HRS-1 predicted mortality.

Conclusions

Both AKI and CKD are common in hospitalized patients with cirrhosis, often occurring simultaneously. Type 2 HRS was not identified, suggesting that its diagnostic criteria may need reevaluation or that this syndrome may not represent a unique functional kidney disorder.
The 5α-Androstanedione Pathway to Dihydrotestosterone in Castration-Resistant Prostate Cancer
Authors: Sharifi Nima
Published: May 2016

The survival and progression of prostate cancer are generally dependent on expression of the androgen receptor (AR), as well as the availability of endogenous AR agonists. Originating from the gonads, testosterone is released into circulation and is converted by steroid-5α-reductase in prostate cancer to 5α-dihydrotestosterone (DHT), potently activating AR and driving tumor progression. Advanced prostate cancer is initially treated with gonadal testosterone depletion, which suppresses this cascade of events and typically leads to a treatment response. Eventually, resistance to testosterone deprivation occurs with “castration-resistant” prostate cancer (CRPC) and is driven by the intratumoral synthesis of DHT. The generation of DHT occurs in large part from adrenal 19-carbon precursor steroids, which are dependent on expression of CYP17A1. Although the path from adrenal precursor steroids to DHT was generally thought to require 5α-reduction of testosterone, recent data suggest that it instead involves conversion from Δ4-androstenedione by steroid-5α-reductase isoenzyme-1 to 5α-androstanedione, followed by subsequent conversion to DHT. The 5α-androstanedione pathway to DHT therefore bypasses testosterone entirely. Abiraterone acetate effectively inhibits CYP17A1, blocks the synthesis of androgens, and extends the survival of men with CRPC. Further progress in the hormonal treatment of CRPC is dependent on an understanding of the mechanisms that underlie CRPC and resistance to abiraterone acetate.
Comorbidities in Gouty Arthritis
Authors: Marwah Rajendra K.
Published: May 2016

Background

Gouty arthritis is increasing in prevalence in men and women, particularly in older age groups.

Methods

A PubMed search was conducted to identify common comorbidities associated with gouty arthritis, their impact on quality of life, and strategies to manage gouty arthritis and its associated comorbidities.

Results

Gouty arthritis is associated with numerous comorbidities that are increasing in prevalence (chronic kidney disease [CKD], hypertension, obesity, diabetes, metabolic syndrome, and cardiovascular disease) and that negatively impact long-term prognosis and quality of life. Therefore, certain considerations and precautions are necessary when treating gouty arthritis in these patients. For example, nonsteroidal anti-inflammatory drugs can cause acute renal toxicity or worsen CKD and should be avoided in this population. Dosage adjustments are recommended when using colchicine and urate-lowering therapy in patients with CKD, which may limit efficacy. Febuxostat may be used in patients with mild to moderate renal impairment, but insufficient information is available for use in patients with creatinine clearance of less than 30 mL/min. Numerous drug-drug interactions in patients with gouty arthritis and comorbidities may alter serum uric acid levels. Several interleukin 1β inhibitors, which target the underlying inflammatory mechanism of gouty arthritis and many of its comorbidities, are in development and may provide an option for patients not adequately managed with other treatments.

Conclusions

Gouty arthritis is associated with renal, metabolic, and cardiovascular comorbidities that negatively impact overall health. The management of gouty arthritis in the presence of comorbidities is particularly challenging because of contraindications, the need for dosage adjustments, and polypharmacy.
The Safety and Efficacy of Etanercept on Cardiac Functions and Lipid Profile in Patients with Active Rheumatoid Arthritis
Authors: Senel Soner , Cobankara Veli , Taskoylu Ozgur , Karasu Ugur , Karapinar Hekim , Erdis Eda , Evrengul Harun , Kaya Mehmet Gungor
Published: May 2016

Objectives

Patients with rheumatoid arthritis (RA) are known to be at increased cardiovascular risk. Etanercept is a tumor necrosis factor α (TNF-α) blocking agent that has been successfully used in the treatment of RA. We sought to assess the effects of etanercept on cardiac functions and lipid profile in RA patients without overt cardiac disease.

Methods

Sixteen patients with active RA were recruited to the study prospectively. Etanercept was administered subcutaneously twice a week for 6 months. Clinical and laboratory predictors of RA activity and lipid profile were evaluated at baseline and at 6 months. The systolic and diastolic function parameters of the left ventricle were obtained by echocardiographic examination and included mitral inflow Doppler and tissue Doppler imaging.

Results

Sixteen patients (13 women; median age, 48 years [range, 27–69 years]) completed the study. Patients’ 28-item Disease Activity Score and Health Assessment Questionnaire scores were significantly reduced by treatment (6.35 to 4.45 [ P < 0.001] and 2.0 to 0.75 [ P = 0.005], respectively). Diastolic dysfunction was detected in 6 patients (37.5%) (3 in grade 1 and 3 in grade 2) by mitral inflow Doppler and the tissue Doppler parameters before the treatment. No significant change in diastolic dysfunction was observed during follow-up (6/16 to 5/16, P = 0.164). In addition, there were also no significant differences in the left ventricular ejection fraction (65.8–66.9, P = 0.168) and lipid profiles after 6 months of etanercept treatment.

Conclusions

Etanercept treatment was safe for use as regards cardiac functions and lipid profiles and effective on RA parameters during 6-month follow-up in patients with active RA.
Influence of Dietary Sodium Modulation on Electrocardiographic Voltage Criteria for Left Ventricular Hypertrophy in Normotensive Individuals
Authors: Larson Carol , Vaidya Anand , Sun Bei , Williams Jonathan S.
Published: May 2016

Objective

Dietary sodium intake and left ventricular hypertrophy (LVH) on electrocardiogram (ECG) are both independent determinants of cardiovascular risk. Prior studies demonstrated that acute dietary sodium modulation significantly altered LVH-specific ECG voltage in hypertensive individuals, thus modifying cardiovascular risk prediction; but whether this phenomenon exists in normotensive individuals is not known. We evaluated the influence of dietary sodium intake on ECG voltage and ECG criteria for LVH in normotensive individuals.

Methods

Retrospective evaluation of ECGs of healthy normotensive individuals (n = 39) who were prospectively randomized to a dietary study protocol of 1 week of high-sodium diet (>200 mmol of sodium per day) and 1 week of low-sodium diet (<10 mmol/d) was conducted. Electrocardiogram voltage amplitudes and biochemical assessments were performed at the end of each dietary intervention.

Results

As expected, blood pressure declined and measures of circulating renin-angiotensin-aldosterone system activity rose significantly with low-sodium diet. No significant changes in specific LVH voltage criteria or overall precordial or limb lead ECG voltage amplitudes were detected between diets.

Conclusion

Although immediate dietary sodium modulation has been shown to significantly alter LVH-specific ECG voltage and the detection of LVH in hypertensive individuals, dietary sodium intake did not influence ECG voltage in normotensive individuals. Healthy normotensive individuals may exhibit adaptive measures that dampen ECG voltage fluctuations in response to dietary sodium modulation. More specific cardiac imaging studies may provide additional insight into this observation and the influence of dietary sodium in cardiac health.
G1359A Polymorphism in the Cannabinoid Receptor-1 Gene is Associated with the Presence of Coronary Artery Disease in Patients with Type 2 Diabetes
Authors: Wang Rui , Hu Wenchao , Qiang Lu
Published: May 2016

Objective

Previous studies demonstrated that G1359A polymorphism of cannabinoid receptor-1 (CNR1) was associated with cardiovascular risk factors including obesity, insulin resistance, dyslipidemia, and inflammation, which are also risk factors for developing type 2 diabetes mellitus (T2DM). Therefore, this study was aimed to determine whether G1359A polymorphism of CNR1 is associated with T2DM and the presence of coronary artery disease (CAD) in patients with T2DM.

Methods

A total of 450 patients with T2DM (259 patients with CAD and 191 patients without CAD) and 94 healthy subjects were genotyped using polymerase chain reaction and restriction fragment length polymorphism method.

Results

No significant differences in genotype frequency of CNR1 were found between normal controls and patients with T2DM without CAD. GG genotype frequency of CNR1 was significantly higher in the patients with T2DM with CAD compared with those without CAD and healthy subjects ( P = 0.003 and P = 0.005, respectively). Unconditional logistic regression analysis revealed that GG genotype was significantly associated with the presence of CAD in the patients with T2DM compared with GA and AA genotypes (odds ratio, 2.632; 95% confidence interval, 1.481–4.678; P < 0.001). In addition, GG genotype of CNR1 was significantly correlated with elevated levels of body mass index, systolic blood pressure, homeostasis model assessment of insulin resistance, and C-reactive protein, as well as decreased levels of high-density lipoprotein cholesterol in patients with T2DM.

Conclusions

G1359A polymorphism of CNR1 may be not associated with T2DM but may contribute to the genetic risk for the presence of CAD in patients with T2DM of Chinese Han population.
Prognostic Significance of Neutrophil Gelatinase–Associated Lipocalin in ST-Segment Elevation Myocardial Infarction
Authors: Akcay Adnan Burak , Ozlu Mehmet Fatih , Sen Nihat , Cay Serkan , Ozturk Oktay Hasan , Yalıcn Fatih , Bilen Perihan , Kanat Selcuk , Karakas Mehmet Fatih , Isleyen Ahmet , Demir Ahmet Duran , Sogut Sadik , Covic Adrian , Kanbay Mehmet
Published: May 2016

Objectives

This study investigated the prognostic value of neutrophil gelatinase–associated lipocalin (NGAL) in patients with ST-segment elevation myocardial infarction (STEMI).

Background

Neutrophil gelatinase–associated lipocalin is a promising biomarker for acute kidney injury. Recently, it was concluded that NGAL may be used beyond the boundaries of renal physiopathology. It was found to be an important factor indirectly contributing to the inflammatory processes. Little is known regarding its predictive role in STEMI.

Methods

One hundred six consecutive patients who underwent percutaneous coronary intervention (PCI) for STEMI and control group consisted of age- and sex-matched 60 consecutive patients with chest pain admitted to the hospital for elective PCI. According to median NGAL level, patients were classified into high- and low-NGAL groups.

Results

Neutrophil gelatinase–associated lipocalin levels were higher in patients with STEMI compared to the elective PCI group subjects. Inhospital and 1-year mortality rates were found to be significantly greater in patients with high NGAL. In addition, inhospital and 1-year major adverse cardiovascular event rates were significantly greater in the high-NGAL group, compared to the low NGAL group. High NGAL level on admission was a significant predictor for long-term mortality and major adverse cardiovascular events. The receiver operating characteristics curve analysis further illustrated that NGAL level on admission is a strong indicator of mortality, with an area under the curve of 0.76 (95% confidence interval, 0.62–0.89).

Conclusions

High NGAL levels may be associated with poor prognosis after PCI in patients with STEMI. However, further studies with larger numbers of patients and longer follow-up are required to evaluate the usefulness of plasma NGAL level for predicting prognosis of STEMI.
FTO Gene Polymorphisms and Platelet Counts in a General Japanese Population
Authors: Kotani Kazuhiko , Fujiwara Shinji , Tsuzaki Kokoro , Sakane Naoki
Published: May 2016

The fat mass and obesity-associated (FTO) gene has recently attracted attention as one of the obesity-related genes. Obesity-related gene polymorphisms may be associated with the development of atherothrombosis in relation to platelets. The present study investigated the association between FTO gene polymorphisms (rs1558902, T/A) and hematological parameters, in particular the platelet counts. Anthropometric, hematological, and biochemical parameters, in addition to genotyping by an allele-specific DNA assay, were measured in 209 asymptomatic community-dwelling Japanese subjects (male/female: 80/129; mean age, 65 years; mean [SD] body mass index, 24.0 [3.0] kg/m2). The subjects with the A-allele (n = 73) showed significantly higher platelet counts than those without the A-allele (mean [SD], 237 [58] vs 217 [57] × 109/L, P < 0.05). Even when multiple-adjusted analyses were performed, the platelet counts continued to differ significantly and independently of other variables, including obesity-related parameters such as the index of insulin resistance or high-sensitivity C-reactive protein, between the subjects with and without the A-allele. The FTO gene polymorphisms may be associated with the minor but significant modulation of platelet counts in this population.
Human Steroid Biosynthesis for the Oncologist
Authors: Auchus Mary Louise , Auchus Richard J.
Published: May 2016

In 2005, results from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial ushered in a new era of endocrine therapy for hormone-responsive malignancies. This study demonstrated that, compared with tamoxifen (a selective estrogen receptor modulator), anastrozole (aromatase inhibitor [AI]) prolonged time to recurrence and disease-free survival for postmenopausal women with breast cancer. The advantage was even greater for those with estrogen receptor–positive (ER+) tumors, and anastrozole was better tolerated than tamoxifen. Since then, AIs have become first-line adjuvant therapy for ER+ breast cancer in postmenopausal women.

In late 2010, a trial comparing abiraterone acetate (a 17-hydroxylase/17,20-lyase [CYP17A1] inhibitor) plus prednisone versus prednisone alone in men with castration-resistant prostate cancer (CRPC) previously treated with docetaxel chemotherapy was terminated early because of the survival benefit in the abiraterone acetate arm. This result not only validated a new therapy for CRPC but also, with the antecedent phase I-II abiraterone studies, shattered our understanding of the molecular mechanisms underpinning CRPC development and progression.

Aromatase inhibitors and CYP17A1 inhibitors will be widely used by oncologists, yet fellowship programs provide little training in steroid biosynthesis, compared with training in the biology of standard chemotherapies. Consequently, these drugs might be used without an appreciation of their caveats and pitfalls. The purpose of this review was to acquaint practicing oncologists with the fundamental principles and pathways of steroid biosynthesis, to improve their understanding of how and why these drugs work, and to alert these physicians to potential problems related to the drugs’ mechanisms of action.
Performance of Bioelectrical Impedance Analysis in the Diagnosis of Metabolic Syndrome
Authors: Ozhan Hakan , Alemdar Recai , Caglar Onur , Ordu Serkan , Kaya Ahmet , Albayrak Sinan , Turker Yasin , Bulur Serkan ,   MELEN Investigators
Published: May 2016

Objective

Central obesity is a prerequisite for the diagnosis of metabolic syndrome (MetS). Precise measurement of visceral fat by bioelectrical impedance analysis (BIA) has been validated. The aim of this study was to investigate the diagnostic performance of BIA in MetS and validate the best cutoff in a large adult cohort.

Materials and Methods

The study was performed on the MELEN Study cohort—a prospectively designed survey on the prevalence of cardiometabolic risk factors in Turkish adults. The final cohort consisted of 2219 participants. Weight and visceral body composition were measured without shoes in light indoor clothes using a bioimpedance analyzer (Omron BF 510; Omron Corp, Kyoto, Japan). Plasma concentrations of cholesterol, insulin, fasting triglycerides, high-density lipoprotein cholesterol, glucose, and other biochemical variables were measured. The diagnostic performance of visceral fat measurement by BIA in patients with MetS was assessed.

Results

Metabolic syndrome was detected in 751 participants (520 women and 231 men with a mean age of 55 [12] years; 34% of the whole study population). Total body fat and visceral fat levels were higher in subjects with MetS. Correlation analyses showed that there were significant correlations between anthropometric and BIA measurements. Receiver operating curve characteristics of visceral adiposity revealed the best cutoff values as greater than 12% for men and greater than 9% for women. The diagnostic performance was good in both sexes (the sensitivity/specificity and area-under-the-curve values were 76%/75% and 0.83 for men and 83%/67% and 0.81 for women, respectively).

Conclusions

Visceral fat measured with BIA is an easily applicable and useful method for identifying people with MetS. The best cutoff values were higher than 12% for men and higher than 9% for women.
Regulation of Cerebral Cholesterol Metabolism in Alzheimer Disease
Authors: Reiss Allison B. , Voloshyna Iryna
Published: May 2016

Alzheimer disease (AD) is an age-related neurodegenerative disorder that manifests as a progressive loss of memory and deterioration of higher cognitive functions. Alzheimer disease is characterized by accumulation in the brain of the β-amyloid peptide generated by β- and γ-secretase processing of amyloid precursor protein. Epidemiological studies have linked elevated plasma cholesterol and lipoprotein levels in midlife with AD development. Cholesterol-fed animal models exhibit neuropathologic features of AD including accumulation of β-amyloid peptide. Specific isoforms of the cholesterol transporter apolipoprotein E are associated with susceptibility to AD. Although multiple lines of evidence indicate a role for cholesterol in AD, the exact impact and mechanisms involved remain largely unknown. This review summarizes the current state of our knowledge of the influence of cholesterol and lipid pathways in AD pathogenesis in vitro and in vivo.
Prevalence of Fibromyalgia Syndrome in Patients Referred to a Tertiary Pain Clinic
Authors: Brill Silviu , Ablin Jacob N. , Goor-Aryeh Itay , Hyat Kim , Slefer Alexander , Buskila Dan
Published: May 2016

Background

Fibromyalgia syndrome (FMS), the prototypical central pain augmentation syndrome, is characterized by widespread pain and tenderness. Although patients referred to tertiary care pain clinics are recognized as suffering from chronic pain, they are generally considered to have pain attributable to discrete peripheral, nociceptive, or neuropathic etiology. The purpose of the current study was to assess the prevalence of FMS among consecutive patients referred to a tertiary pain clinic and to evaluate the contribution of central pain to the clinical impact upon such patients.

Methods

Eighty-five consecutive patients (38 were male, and 47 were female) attending a pain clinic were assessed for the presence of FMS. The presence of FMS was determined according to the 1990 American College of Rheumatology (ACR) classification criteria. Quality of life and physical functioning were assessed, utilizing a structured questionnaire.

Results

The ACR criteria for the classification of FMS were fulfilled by 41.2% of patients. Patients fulfilling FMS criteria ranked significantly lower on all domains of the SF-36, including general health, physical functioning, role limitation due to physical and emotional problems, vitality, social functioning, bodily pain, and mental health. Composite physical and mental health scores were significantly lower among patients fulfilling ACR FMS criteria. Patients fulfilling the ACR criteria for FMS felt significantly more tenderness, based on the mean number of tender points and the mean tenderness threshold, when compared with patients not fulfilling the ACR FMS criteria.

Conclusions

A significant proportion of patients referred to a tertiary pain clinic were found to fulfill the ACR criteria for classification of FMS and thus exhibit an important element of central pain. Central pain augmentation should be actively searched for and therapeutically addressed in the evaluation and management of all patients with chronic pain.
Sex Differences in Cardiovascular Disease Risk and Exercise in Type 2 Diabetes
Authors: Miller Tyler M. , Gilligan Sarah , Herlache Leah L. , Regensteiner Judith G.
Published: May 2016

Diabetes currently affects approximately 14% of the US population, and cardiovascular disease (CVD) is a leading cause of morbidity and mortality in those with diabetes. Although in the general population women are at lower risk than men for CVD, women have a disproportionately greater increase in risk for CVD than do men in the context of diabetes. Physical activity is considered a cornerstone in the prevention and treatment of CVD and its risk factors, but greater barriers to physical activity may exist for women with diabetes compared to their male counterparts. In this article, we review sex differences in CVD incidence and risk among diabetics, sex differences in physical activity behaviors, cardiovascular abnormalities and impaired exercise capacity in women living with diabetes, and the effects of exercise on prevention and treatment of CVD in diabetic women. Finally, we discuss future research needed to clarify potential sex differences in the cardiovascular effects of diabetes and to establish ways to reduce the barriers to exercise in women with diabetes.
The Relationship between High-Density Lipoprotein Cholesterol and Coronary Collateral Circulation in Patients with Coronary Artery Disease
Authors: Kadi Hasan , Ozyurt Huseyin , Ceyhan Koksal , Koc Fatih , Celik Atac , Burucu Turgay
Published: May 2016

Introduction

High-density lipoprotein cholesterol (HDL-C) promotes cholesterol efflux from macrophage foam cells in atheroma plaques. In addition, HDL-C has anti-inflammatory and endothelium-protective properties. Despite that the only prerequisite for collateral development is shown to be the degree of coronary artery stenosis, there are significant differences even among patients with a similar degree of coronary artery disease.

Objective

We designed this study to investigate a possible association between HDL-C and coronary collateral circulation (CCC).

Materials and Methods

All study participants had at least one occluded major coronary artery. Demographic, clinical, and laboratory data were obtained from patients’ medical records. To classify CCC, we used Rentrop classification. The patients were then classified as having poor CCC (Rentrop grades 0–1) or good CCC (Rentrop grades 2–3). We performed t test and the χ2 test in comparing groups and multivariate logistics regression analysis to determine the predictors of CCC. The study population consisted of 151 patients (mean age, 63.7 ± 9 years; 76.2% male).

Results

Forty-nine patients had poor CCC and 102 patients had good CCC. The proportion of previous myocardial infarctions, serum triglycerides, and low HDL-C levels were more frequent in the poor CCC group ( P = 0.026, P = 0.015, and P < 0.001, respectively). Multivariate logistic regression analysis revealed that low HDL-C is a predictor of CCC ( B = 1.456; P < 0.001; odds ratio, 4.3; 95% confidence interval, 1.964–9.369).

Conclusion

We found that low HDL-C frequency was more frequent in the poor CCC group than the good CCC group, and HDL-C was a predictor of CCC.
Antiplatelet Therapy for Secondary Prevention of Acute Coronary Syndrome, Transient Ischemic Attack, and Noncardioembolic Stroke in an Era of Cost Containment
Authors: Kessler Chad , Thomas Kurian , Kao John
Published: May 2016

Physicians are aware of the profound impact of oral antiplatelet therapy for secondary prevention of acute coronary syndrome (ACS), transient ischemic attack, and noncardioembolic stroke. Numerous clinical studies have compared the benefits of aspirin (ASA) alone with those of combination therapy with extended-release dipyridamole or with those of clopidogrel, with or without ASA, for secondary stroke prevention; and of ASA monotherapy compared with ASA plus clopidogrel combination therapy for secondary prevention in various ACS populations. More recently, ASA plus prasugrel has been compared with ASA plus clopidogrel in a high-risk ACS population. However, given the different treatment modalities and methods used in the various trials, it is difficult to make generalizations as to which therapy is most effective with the lowest risk of bleeding. Further complicating physician's decision making are cost considerations, particularly with the newer oral antiplatelet agents, which are considerably more expensive than ASA. This review provides a brief overview of the clinical data on each of the currently marketed oral antiplatelet agents and the available data on cost-effectiveness for the secondary prevention of ACS, transient ischemic attack, and noncardioembolic stroke.
Placental Protein 13 as an Early Predictor in Egyptian Patients with Preeclampsia, Correlation to Risk, and Association with Outcome
Authors: El Sherbiny Walid S. , Soliman Ahmed , Nasr Aml S.
Published: May 2016

Introduction

Placental protein 13 (PP13) is a protein expressed only in the placenta. It is involved in gluing the placenta to the uterus and remodeling the maternal arteries to expand them. Women who subsequently develop preterm preeclampsia have low first trimester maternal serum.

Aim of Work

The aim of this work was to assess the value of PP13 as an early marker for screening of preeclampsia and to correlate it with the PP13 messenger RNA (mRNA).

Patients and Methods

As a part of the Antenatal Screening Project, 100 women in the first trimester of pregnancy were selected and subdivided into 2 groups: 50 women who developed preeclampsia in their third trimester (patient group) and 50 women who completed normal uncomplicated pregnancy until full term (control group). Placental protein 13 level was measured using the commercially available enzyme-linked immunosorbent assay kit and PP13 mRNA was tested using reverse transcription polymerase chain reaction.

Results

The maternal serum PP13 level in the preeclamptic group was (157.9 ± 45.5 pg/mL), which is significantly lower than that of the control group (225.3 ± 67.3 pg/mL), with highly statistically significant difference ( P < 0.0001). The frequency of maternal PP13 mRNA expression was lower in the preeclamptic group (28%) compared to that in the control group (76%), with highly statistically significant difference ( P < 0.0001).

Conclusion

Combined serum PP13 level assay and PP13 mRNA expression are reliable markers for early detection of preeclampsia, and we recommend doing it as a routine investigation during the first trimester.
Collaboration and Team Science: From Theory to Practice
Authors: Bennett L. Michelle , Gadlin Howard
Published: May 2016

Interdisciplinary efforts are becoming more critical for scientific discovery and translational research efforts. Highly integrated and interactive research teams share a number of features that contribute to their success in developing and sustaining their efforts over time. Through analysis of in-depth interviews with members of highly successful research teams and others who did not meet their goals or ended because of conflicts, we identified key elements that are critical for team success and effectiveness. There is no debate that the scientific goal sits at the center of the collaborative effort. However, supporting features need to be in place to avoid the derailment of the team. Among the most important of these is trust: without trust, the team dynamic runs the risk of deteriorating over time. Other critical factors of which both leaders and participants need to be aware include developing a shared vision, strategically identifying team members and purposefully building the team, promoting disagreement while containing conflict, and setting clear expectations for sharing credit and authorship. Self-awareness and strong communication skills contribute greatly to effective leadership and management strategies of scientific teams. While all successful teams share the characteristic of effectively carrying out these activities, there is no single formula for execution with every leader exemplifying different strengths and weaknesses. Successful scientific collaborations have strong leaders who are self-aware and are mindful of the many elements critical for supporting the science at the center of the effort.
Angiotensin II–Mediated Left Ventricular Abnormalities in Chronic Kidney Disease
Authors: Raizada Veena , Hillerson Dustin , Amaram Jaya Sheela , Skipper Betty
Published: May 2016

Angiotensin II (ATII), the biologically active product of the renin-angiotensin system (RAS), is involved in modulation of left ventricular (LV) structure and function in chronic kidney disease (CKD). Because the RAS system is overactive in CKD, excess ATII accumulates in the heart, thereby promoting myocyte hypertrophy, fibroblast proliferation, interstitial accumulation of collagen, and microvessel disease. These cardiac abnormalities are further enhanced by a possible interaction between enhanced RAS activity and hypercalcemia, hyperphosphatemia and secondary hyperparathyroidism, and vitamin D deficiency. The ATII-associated stimulation of aldosterone production from the adrenal gland and the increase in activity of the sympathetic system in CKD, further contribute to LV abnormalities. Myocardial structural changes are major determinants of an increase in myocardial stiffness, leading to LV diastolic and systolic function impairment, and clinical congestive heart failure. Other complications include cardiac conduction disturbances, QT prolongation, and arrhythmias, which all contribute to elevated cardiovascular mortality in patients with CKD.
Vitamin D Deficiency is Associated with the Development of Subclinical Coronary Artery Disease in African Americans with HIV Infection: A Preliminary Study
Authors: Lai Hong , Detrick Barbara , Fishman Elliot K. , Gerstenblith Gary , Brinker Jeffrey A. , Hollis Bruce W. , Bartlett John , Cofrancesco Joseph , Tong Wenjing , Tai Hong , Chen Shaoguang , Bhatia Sandeepan , Lai Shenghan
Published: May 2016

Background

Premature coronary artery disease (CAD) is a major concern in human immunodeficiency virus (HIV)-infected African Americans. The objectives of the study were to estimate the incidence of subclinical CAD, defined by the presence of coronary plaque and/or calcification on cardiac computed tomography (CT), and to identify the associated risk factors in this vulnerable population.

Subjects and Methods

Between August 2003 and September 2010, 188 HIV-infected African Americans without known, or symptoms of, CAD underwent cardiac CT. The subset without demonstrable disease underwent a second cardiac CT approximately 2 years later. The incidence of disease over that period and the effects of antiretroviral treatment and other known and hypothesized risk factors were investigated.

Results

Sixty-nine of these 188 African Americans had evidence of subclinical disease on the initial cardiac CT, confirming prior high prevalence reports. A second cardiac CT was performed on 119 African Americans without disease approximately 2 years later. The total person-years of follow-up was 284.4. Subclinical CAD was detected in 14 of these, yielding an overall incidence of 4.92/100 person-years (95% confidence interval, 2.69–8.26). Among the factors investigated, only male sex and vitamin D deficiency were independently associated with the development of subclinical CAD. The study did not find significant associations between CD4 count, HIV viral load, antiretroviral treatment use, or cocaine use and the incidence of subclinical CAD.

Conclusions

The incidence of subclinical CAD in African Americans with HIV infection is provocatively high. Larger studies are warranted to confirm the role of vitamin D deficiency in the development of CAD in HIV-infected African Americans.
Serum Vitamin D Levels are Independently Associated with Severity of Coronary Artery Disease
Authors: Akin Fatih , Ayça Burak , Köse Nuri , Duran Mustafa , Sarı Mustafa , Uysal Onur Kadir , Karakukcu Cigdem , Arinc Huseyin , Covic Adrian , Goldsmith David , Okçün Barış , Kanbay Mehmet
Published: May 2016

Background and Objectives

Low-serum vitamin D levels have been associated with increased cardiovascular risk in the general population. We hypothesized that serum vitamin D levels would be inversely associated with inflammation and with severity of coronary atherosclerosis. We therefore investigated the link between serum vitamin D levels and (1) the extent of coronary artery disease (CAD) assessed by the Gensini score and (2) inflammatory parameters, including C-reactive protein and fibrinogen.

Materials and Methods

We measured 25-hydroxyvitamin D (25[OH]D) and inflammatory markers in 239 patients who underwent coronary angiography. We analyzed the relation between serum levels of 25(OH)D and inflammatory markers and angiographic severity of CAD. The Gensini lesion severity score was used for assessing the severity of coronary atherosclerosis.

Results

Vitamin D insufficiency was very common among our study population: 83% of the study population had levels less than 30 ng/mL. The Gensini score was negatively associated with serum vitamin D levels ( r = −0.416, P < 0.001), and positively correlated with age ( r = 0.209, P = 0.001), blood pressure ( r = 0.379, P < 0.001), diabetes ( r = 0.335, P < 0.001), hyperlipidemia ( r = 0.150, P = 0,021), and C-reactive protein levels ( r = 0.214, P = 0,001). After adjustments for traditional and nontraditional cardiovascular risk factors, vitamin D (B = −0,345, P < 0,001) remained a significant predictor for the severity of CAD.

Conclusions

Low-serum 25(OH)D levels are associated with the severity of coronary artery stenosis. Further studies are warranted to determine whether vitamin D supplementation could prevent progression of CAD.