bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Gene Expression in Cholesteatoma by DNA Chip Analysis
Authors: Macias John D. , Gerkin Richard D. , Locke Darren , Macias MiMi P. 
Published: May 2013

Objectives/HypothesisIn contrast to normal epithelium, the desquamating stratified squamous epithelium of temporal bone cholesteatoma characteristically exhibits sustained hyperproliferative growth and a capacity for bone erosion. We conducted genome‐wide microarray analyses to determine the molecular nature of cholesteatoma's biological processes and identify disease‐associated, altered gene activity. We tested the hypothesis that genes contributing to the pathophysiology of cholesteatoma are differentially expressed compared to control tissue.Study DesignProspective experimental analysis.MethodsUsing new, enhanced microarray platforms and well‐annotated human transcriptome probes, we measured global gene expression levels in surgical specimens of cholesteatoma and in the corresponding normal postauricular skin in four patients. Genes of interest were verified by quantitative real time reverse transcriptase polymerase chain reaction analyses using cholesteatoma and postauricular sample pairs (n = 13). External auditory canal skin from six additional patients was also evaluated as a normal control. Immunohistochemistry detected protein expression in tissue sections and the cells involved.ResultsDNA chip analyses identified 282 differentially expressed genes in cholesteatoma compared to control samples. Of these, 104 genes were upregulated and 178 were downregulated. Ontological classifications indicate relationships to cellular processes including receptor binding, cell communication and motion, vitamin metabolism, and cytokine‐mediated inflammation. Based on potential involvement in disease pathology, 10 genes were selected and independently verified by quantitative polymerase chain reaction. Immunohistochemical detection of transcobalamin‐1 and CCL27 implicates cholesteatoma keratinocytes and dermal endothelial cells as contributors in disease processes.ConclusionsWe present a comprehensive, human genome‐wide survey of disease‐associated gene expression that extends the public database and provides new evidence for molecular mechanisms involved in cholesteatoma pathology. Laryngoscope, 123:S1–S21, 2013
Antibodies directed against integration host factor mediate biofilm clearance from nasopore
Authors: Brandstetter Kathleyn A. , Jurcisek Joseph A. , Goodman Steven D. , Bakaletz Lauren O. , Das Subinoy 
Published: May 2013

Objectives/HypothesisIntranasal resorbable packing, such as Nasopore, is commonly used during sinus surgery despite a paucity of evidence that demonstrates clinical benefit. We theorized that Nasopore supports bacterial growth and biofilm formation. The DNABII family of bacterial nucleic acid binding proteins stabilizes the extracellular polymeric substance of the biofilm, thus protecting bacteria from host defenses and traditional antibiotics. We tested the hypothesis that use of anti‐IHF antibodies in conjunction with antibiotics would enhance biofilm eradication from Nasopore.Study DesignIn vitro experiments.MethodsNontypeable Haemophilus influenzae (NTHI) biofilms were grown on Nasopore. Following 24‐hour incubation, biofilms were incubated for an additional 16 hours with either medium alone, naïve rabbit serum, rabbit anti‐IHF serum, amoxicillin/clavulanate, or anti‐IHF serum + amoxicillin/clavulanate. Computer statistics (COMSTAT) analysis was performed on images of biofilms obtained via confocal microscopy.ResultsNTHI readily formed a biofilm on Nasopore. Treatment with amoxicillin/clavulanate alone mediated an increase in biomass by 92% to 6.63 μ2/μ3 compared to incubation in sterile medium alone (3.46 μ2/μ3). Treatment with anti‐IHF alone reduced the biomass by 77% to 1.29 μ2/μ3 compared to incubation with naïve rabbit serum (5.53 μ2/μ3). Anti‐IHF + amoxicillin/clavulanate reduced biomass by 88% to 0.66 μ2/μ3 (P <0.02) compared to incubation with naïve rabbit serum.ConclusionAntibiotics alone were ineffective in eradicating NTHI biofilms that had formed on Nasopore in vitro. Anti‐IHF antibodies plus amoxicillin/clavulanate therapy synergistically reduced biofilm biomass by 88%. These data support clinical studies for the use of anti‐IHF combined with antibiotics to reduce biofilm formation on intranasal packing.Level of EvidenceN/A. Laryngoscope, 123:2626–2632, 2013
Depressive symptoms are associated with visceral adiposity in a community‐based sample of middle‐aged women and men
Authors: Murabito Joanne M. , Massaro Joseph M. , Clifford Brian , Hoffmann Udo , Fox Caroline S. 
Published: May 2013

ObjectiveTo examine the relation between measures of adiposity and depressive symptoms in a large well characterized community‐based sample, we examined the relations of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) to depressive symptoms in 1,581 women (mean age 52.2 years) and 1,718 men (mean age 49.8 years) in the Framingham Heart Study.Design and MethodsDepressive symptoms were measured using the Center for Epidemiologic Studies Depression (CES‐D) scale. Regression models were created to examine the association between each fat depot (exposure) and depressive symptoms (outcome). Sex‐specific models were adjusted for age, body mass index, smoking, alcohol consumption, diabetes, hypertension, total and HDL cholesterol, lipid lowering treatment, CVD, menopause, C‐reactive protein, and physical activity.ResultsMean CES‐D scores were 6.8 and 5.6 in women and men. High levels of depressive symptoms were present in 22.5% of women and 12.3% of men. In women, one standard deviation increase in VAT was associated with a 1.3 point higher CES‐D score after adjusting for age and BMI (P < 0.01) and remained significant in the fully adjusted model (P = 0.03). The odds ratio of depressive symptoms per 1 standard deviation increase in VAT in women was 1.33 (P = 0.015); results were attenuated in fully adjusted models (OR 1.29, P = 0.055). In men, the association between VAT and CES‐D score and depressive symptoms was not significant. SAT was not associated with CES‐D score or depressive symptoms.ConclusionsThis study supports an association between VAT and depressive symptoms in women. Further work is needed to uncover the complex biologic mechanisms mediating the association.
Serum leptin and adiponectin levels and risk of renal cell carcinoma
Authors: Liao Linda M. , Schwartz Kendra , Pollak Michael , Graubard Barry I. , Li Zhen , Ruterbusch Julie , Rothman Nathaniel , Davis Faith , Wacholder Sholom , Colt Joanne , Chow Wong‐Ho , Purdue Mark P. 
Published: May 2013

ObjectiveThe incidence of renal cell carcinoma (RCC) has increased rapidly in the U.S., particularly among African Americans. Despite a well‐established link between obesity and RCC, the mechanism through which obesity increases cancer risk has yet to be established. Adipokines, such as leptin and adiponectin, may link obesity and cancer, with different quantitative effects by race.Design and MethodsWe evaluated the association between leptin and adiponectin concentrations and RCC risk among Caucasians (581 cases, 558 controls) and African Americans (187 cases, 359 controls) in a case‐control study conducted in Detroit and Chicago. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated using unconditional logistic regression.ResultsAmong controls, Caucasians had higher median adiponectin than African Americans (males: 8.2 vs. 7.0 μg/ml, P = 0.001; females: 13.4 vs. 8.4 μg/ml, P < 0.0001), and lower median leptin than African Americans (males: 11.8 vs. 14.1 ng/ml, P = 0.04; females: 28.3 vs. 45.9 ng/ml, P < 0.0001). Among Caucasians, the ORs for RCC comparing the highest (Q4) to the lowest (Q1) sex‐specific quartile of leptin were 3.2 (95% CI: 1.9–5.2) for males and 4.7 (95% CI: 2.6–8.6) for females. Serum leptin was not significantly associated with RCC among African American males (OR 1.5, 95% CI: 0.7–3.1) or females (OR 2.1, 95% CI: 0.8–5.5). Higher adiponectin was associated with RCC risk among African American males (Q4 vs. Q1: OR 2.3, 95% CI: 1.1–4.6) and females (OR 2.1, 95% CI: 1.2–6.7), but not significantly among Caucasian males (OR 1.6, 95% CI: 0.99–2.7) and females (OR 1.6, 95% CI: 0.9–3.1).ConclusionWe observed an association between both leptin and adiponectin concentrations and risk of RCC, which may differ by race. Confirmation in further investigations is needed.
High protein intake stimulates postprandial GLP1 and PYY release
Authors: van der Klaauw Agatha A. , Keogh Julia M. , Henning Elana , Trowse Victoria M. , Dhillo Waljit S. , Ghatei Mohammad A. , Farooqi I. Sadaf 
Published: May 2013

ObjectiveMeals high in protein induce greater intermeal satiety than meals high in fat and carbohydrates. We studied the gut hormone response and subsequent food intake after breakfasts high in protein, carbohydrate or high in fat controlled for volume, calories and appearance.Design and MethodsEight healthy volunteers participated in this randomized three‐way crossover study. Study breakfasts were calculated to provide 20% of daily energy requirements and provided either 60% of energy from protein, fat or carbohydrate. Blood was drawn half‐hourly for 4 h; energy intake at a subsequent ad libitum meal was measured.ResultsTotal ghrelin decreased after food intake equally with the three breakfasts. PYY levels were highest after the high protein breakfast (P = 0.005). Indeed, PYY at 240 min was highest after the high protein breakfast compared to the high fat breakfast and to the high carbohydrate breakfast (P = 0.011 and P = 0.012, respectively). GLP‐1 levels were highest after the high protein breakfast (P = 0.041) at 120 min and remained higher throughout the study. These differences in gut hormones did not translate into differences in food intake (1023 ± 390 kcal after high protein, 1016 ± 388 kcal after high fat and 1158 ± 433 kcal after high carbohydrate).ConclusionWe conclude that a high protein meal increases circulating concentrations of the gut hormones PYY and GLP‐1, but when meals are matched for volume, appearance and caloric value, these gut hormone changes do not translate into a reduction in ad libitum food intake.
College expectations in high school mitigate weight gain over early adulthood: Findings from a national study of American youth
Authors: Clarke Philippa J. , O'Malley Patrick M. , Schulenberg John E. , Lee Hedwig , Colabianchi Natalie , Johnston Lloyd D. 
Published: May 2013

ObjectiveResearch conducted on school‐based interventions suggests that school connectedness protects against a variety of risk behaviors, including substance abuse, delinquency and sedentary behavior. The line of research is extended by examining the link between college expectations and early adult weight gain using nationally representative panel data from thirty cohorts of American high school seniors followed prospectively to age 30 in the Monitoring the Future Study (1986‐2009).Design and MethodsGrowth mixture models identified two latent classes of trajectories of body mass index (BMI) from age 19 to 30: a persistently overweight class (BMI ≥ 25) and a second class exhibiting more moderate growth in BMI to age 30.ResultsCompared to those who did not expect to graduate from college, students fully expecting to graduate from college had 34% lower odds of being in the persistently overweight class (adjusted odds ratio = 0.66, 95% confidence interval = 0.54, 0.81), controlling for academic performance and socioeconomic status.ConclusionsSuccessful prevention of obesity early in the life course is based on a multifactorial approach incorporating strategies that address the contexts in which adolescents are embedded. The school setting may be one avenue where successful educational attachment could have positive consequences for subsequent weight gain in early adulthood.
Variants in adiponectin signaling pathway genes show little association with subclinical CVD in the diabetes heart study
Authors: Cox Amanda J. , Lambird John E. , Sandy An S. , Register Thomas C. , Langefeld Carl D. , Carr J.Jeffrey , Freedman Barry I. , Bowden Donald W. 
Published: May 2013

ObjectiveUnderstanding the interplay between adiposity, inflammation, and cardiovascular complications in type 2 diabetes mellitus (T2DM) remains a challenge. Signaling from adipocytes is considered important in this context. Adiponectin is the most abundant adipocytokine and has been associated with various measures of cardiovascular disease (CVD). This study examines the relationships between genetic variants in the adiponectin (ADIPOQ) and adiponectin‐related signaling pathway genes and measures of subclinical CVD (vascular calcified plaque and carotid intima‐media thickness), plasma lipids, and inflammation in T2DM.Design and MethodsSingle‐nucleotide polymorphisms (SNPs) in ADIPOQ (n = 45), SNPs tagging ADIPOR1 (n = 6), APIPOR2 (n = 8), APPL1 (n = 6) and known rare coding variants in KNG1 (n = 3) and LYZL1 (n = 3) were genotyped in 1220 European Americans from the family‐based Diabetes Heart Study. Associations between SNPs and phenotypes of interest were assessed using a variance components analysis with adjustment for age, sex, T2DM‐affected status, and body mass index.ResultsThere was minimal evidence of association between SNPs in the adiponectin signaling pathway genes and measures of calcified plaque; eight of the 71 SNPs showed evidence of association with subclinical CVD (P = 0.007‐0.046) but not with other phenotypes examined. Nine additional SNPs were associated with at least one of the plasma lipid measures (P = 0.008‐0.05).ConclusionFindings from this study do not support a significant role for variants in the adiponectin signaling pathway genes in contributing to risk for vascular calcification in T2DM. However, further understanding the interplay between adiposity, plasma lipids, and inflammation may prove important in the prediction and management of cardiovascular complications in T2DM.
Primary antiphospholipid antibody syndrome—one further aspect of thrombophilia in overweight and obese patients with venous thromboembolism
Authors: Gary Thomas , Belaj Klara , Bruckenberger Rosa , Hackl Gerald , Hafner Franz , Froehlich Harald , Zebisch Armin , Pilger Ernst , Brodmann Marianne 
Published: May 2013

Objective: Overweight and obesity are established risk factors for venous thromboembolism (VTE). We examined the difference in the frequency of primary antiphospholipid antibody syndrome (PAPS) in VTE patients according to their BMI.Design and Methods: We included 998 VTE patients treated at our institution between 2009 and 2011 in a retrospective data analysis. Thrombophilia screening including evaluation for APS (lupus anticoagulant, anti‐cardiolipin, and anti‐B2‐glycoprotein‐I IgG and IgM antibodies) was performed in all patients.Results: PAPS was diagnosed in 6.8% (24/355) of normal weight (BMI < 24 kg/m2) VTE patients, in 11.1% (50/452) of overweight (BMI 25–30 kg/m2) VTE patients, and in 15.7% (30/191) of obese (BMI > 31 kg/m2) VTE patients. The difference of PAPS occurrence between these groups was statistically significant (P = 0.001). PAPS patients demonstrated higher fibrinogen levels as compared to non‐PAPS patients (median 416.0 md/dl vs. 352.0 mg/dl, P = 0.001). Furthermore, fibrinogen levels increased significantly according to the body weight of patients (median normal weight patients 330.0 mg/dl vs. overweight patients 359.0 mg/dl vs. obese patients 415.0 mg/dl, P = 0.001).Conclusion: PAPS seems to be more frequent in overweight and obese patients. As PAPS patients showed significantly higher fibrinogen levels and as fibrinogen levels increased significantly according to the body weight of patients, an elevated inflammatory state in overweight and obese patients as a reason for the increased PAPS occurrence can be assumed.
Doctor shopping by overweight and obese patients is associated with increased healthcare utilization
Authors: Gudzune Kimberly A. , Bleich Sara N. , Richards Thomas M. , Weiner Jonathan P. , Hodges Krista , Clark Jeanne M. 
Published: May 2013

ObjectiveNegative interactions with healthcare providers may lead patients to switch physicians or “doctor shop.” We hypothesized that overweight and obese patients would be more likely to doctor shop, and as a result, have increased rates of emergency department (ED) visits and hospitalizations as compared to normal weight nonshoppers.Design and MethodsWe combined claims data from a health plan in one state with information from beneficiaries' health risk assessments. The primary outcome was “doctor shopping,” which we defined as having outpatient claims with ≥5 different primary care physicians (PCPs) during a 24‐month period. The independent variable was standard NIH categories of weight by BMI. We performed multivariate logistic regression to evaluate the association between weight categories and doctor shopping. We conducted multivariate zero‐inflated negative binominal regression to evaluate the association between weight‐doctor shopping categories with counts of ED visits and hospitalizations.ResultsOf the 20,726 beneficiaries, the mean BMI was 26.3 kg m−2 (SD 5.1), mean age was 44.4 years (SD 11.1) and 53% were female. As compared to normal weight beneficiaries, overweight beneficiaries had 23% greater adjusted odds of doctor shopping (OR 1.23, 95%CI 1.04‐1.46) and obese beneficiaries had 52% greater adjusted odds of doctor shopping (OR 1.52, 95%CI 1.26‐1.82). As compared to normal weight non‐shoppers, overweight and obese shoppers had higher rates of ED visits (IRR 1.85, 95%CI 1.37‐2.45; IRR 1.83, 95%CI 1.34‐2.50, respectively), which persisted during within weight group comparisons (Overweight IRR 1.50, 95%CI 1.10‐2.03; Obese IRR 1.54, 95%CI 1.12‐2.11).ConclusionFrequently changing PCPs may impair continuity and result in increased healthcare utilization.
Androgenic sex steroids contribute to metabolic risk beyond intra‐abdominal fat in overweight/obese black and white women
Authors: Perry Arlette , Wang Xuewen , Goldberg Ronald , Ross Robert , Jackson Loreto 
Published: May 2013

ObjectiveTo determine the independent contribution of androgenic sex hormones beyond visceral adipose tissue (VAT) on metabolic risk.Design and MethodsA cross‐sectional evaluation of 66 (36 white and 30 black) premenopausal overweight/obese women using multiple regression analyses to determine the independent effects of sex hormone‐binding globulin (SHBG), total testosterone (TT), and free testosterone using the free androgen index (FAI) on metabolic variables above VAT.ResultsSHBG contributed to the variance in insulin (P = 0.003), insulin resistance using HOMA‐IR (P = 0.006), and high‐density lipoprotein cholesterol2 (P = 0.029). TT contributed to the variance in systolic and diastolic blood pressure (P < 0.001), total cholesterol (P = 0.003), low‐density lipoprotein cholesterol (P = 0.003), and apolipoprotein B (P = 0.004). FAI contributed to the variance in the greatest number of metabolic variables beyond VAT. There was also a significant race–FAI interaction for fasting glucose (P = 0.013). A Pearson's correlation coefficient showed a significant relationship between FAI and glucose in white women (r = 0.48, P = 0.003) while showing no relationship in black women (r = −0.01, P = 0.941).ConclusionsOur study showed that androgenic sex steroids contributed significantly to the variance in metabolic variables associated with health risk. However, they do not provide sufficient information relevant to glucose status in black women.
Endogenous oxidative stress, but not ER stress, induces hypoxia‐independent VEGF120 release through PI3K‐dependent pathways in 3T3‐L1 adipocytes
Authors: Takahashi Kazuto , Miyokawa‐Gorin Kaoru , Handa Keiko , Kitahara Atsuko , Moriya Rie , Onuma Hirohisa , Sumitani Yoshikazu , Tanaka Toshiaki , Katsuta Hidenori , Nishida Susumu , Yoshimoto Katsuhiko , Ohno Hideki , Ishida Hitoshi 
Published: May 2013

ObjectiveExpressions of vascular endothelial growth factor (VEGF) are increased in obese adipocytes and is secreted from obese adipose tissue through hypoxia‐independent pathways. Therefore, we investigated the hypoxia‐independent mechanism underlying increased expression and release of VEGF in obese adipocytes.Design and MethodsWe compared signal transduction pathways regulating VEGF with those regulating monocyte chemoattractant protein‐1 (MCP‐1), which is increased in obese adipocytes, in an in vitro model of artificially hypertrophied 3T3‐L1 adipocytes preloaded with palmitate, without the influence of hypoxia.ResultsPalmitate‐preloaded cells exhibited significantly enhanced oxidative stress (P < 0.01) and showed increased VEGF120 and MCP‐1 release (P < 0.01, respectively), while endoplasmic reticulum (ER) stress was not induced. Increased VEGF120 release was significantly decreased with PI3K inhibitor LY294002 (P < 0.01). In addition, antioxidant N‐acetyl‐cysteine (NAC) markedly diminished not only VEGF120 secretion (P < 0.01) but also augmented Akt phosphorylation on Ser473 (P < 0.01). In contrast, increased MCP‐1 release was suppressed with JNK inhibitor SP600125 and p38 MAPK inhibitor SB203580 (P < 0.01).ConclusionsVEGF120 release from hypertrophied adipocytes can be enhanced through PI3K pathways activated by oxidative stress but not by ER stress, suggesting that VEGF120 secretion is regulated through oxidative stress‐dependent pathways distinct from those involved in MCP‐1 release through either JNK or p38 MAPK activation.
A synthetic anti‐inflammatory sterol improves insulin sensitivity in insulin‐resistant obese impaired glucose tolerance subjects
Authors: Reading Christopher L. , Stickney Dwight R. , Flores‐Riveros Jaime , Destiche Daniel A. , Ahlem Clarence N. , Cefalu William T. , Frincke James M. 
Published: May 2013

ObjectiveTo study the activity of HE3286 (17α‐ethynylandrost‐5‐ene‐3β,7β,17β‐triol), an anti‐inflammatory sterol that is active in models of obesity‐induced inflammation and insulin resistance in high body mass index (BMI) subjects with impaired glucose tolerance (IGT).Design and MethodsHE3286 was explored in high BMI IGT subjects using hyperinsulinemic, euglycemic clamp studies.ResultsIn insulin‐resistant subjects, HE3286 significantly increased day 29 insulin‐stimulated glucose disposal and HDL cholesterol, and decreased C‐reactive protein (CRP) compared to placebo. For HE3286, change in M value showed a significant negative correlation with baseline M value. Subjects with baseline M value below the median (4.2 mg/kg/min) had significantly lower adiponectin and higher lipopolysaccharide‐stimulated peripheral blood mononuclear cell cytokine secretion. After 28 days of HE3286 treatment, adiponectin levels were significantly increased in insulin‐resistant (baseline M < 4.2), but not insulin‐sensitive (baseline M > 4.2) subjects, compared to placebo.ConclusionsHE3286 significantly increased the frequency of subjects with increased insulin‐stimulated glucose disposal and HDL, and decreased CRP compared to placebo, in insulin‐resistant, but not insulin‐sensitive subjects. Thus, HE3286 may preferentially benefit insulin‐resistant, inflamed, high BMI IGT subjects.