bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory Syncytial Virus Represses Glucocorticoid Receptor-Mediated Gene Activation
Authors: Hinzey Adam , Alexander Jacob , Corry Jacqueline , Adams Kathleen M. , Claggett Amanda M. , Traylor Zachary P. , Davis Ian C. , Webster Marketon Jeanette I. 
Published: December 2010

AbstractRespiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants. Although antiinflammatory in nature, glucocorticoids have been shown to be ineffective in the treatment of RSV-induced bronchiolitis and wheezing. In addition, the effectiveness of glucocorticoids at inhibiting RSV-induced proinflammatory cytokine production in cell culture has been questioned. In this study, we have investigated the effect of RSV infection on glucocorticoid-induced gene activation in lung epithelium-derived cells. We show that RSV infection inhibits dexamethasone induction of three glucocorticoid receptor (GR)-regulated genes (glucocorticoid-inducible leucine zipper, FK506 binding protein, and MAPK phosphatase 1) in A549, BEAS-2B cells, and primary small airway epithelial cells. UV irradiation of the virus prevents this repression, suggesting that viral replication is required. RSV is known to activate the nuclear factor κB (NFκB) pathway, which is mutually antagonistic towards the GR pathway. However, specific inhibition of NFκB had no effect on the repression of GR-induced genes by RSV infection, indicating that RSV repression of GR is independent of NFκB. RSV infection of A549 cells does not alter GR protein levels or GR nuclear translocation but does reduce GR binding to the promoters of the glucocorticoid responsive genes analyzed in this study. Repression of GR by RSV infection may account for the apparent clinical ineffectiveness of glucocorticoids in RSV bronchiolitis therapy. In addition, this data adds to our previously published data suggesting that GR may be a general target for infectious agents. Identifying the mechanisms through which this suppression occurs may lead to the development of novel therapeutics.
Integrin α3, But Not β1, Regulates Islet Cell Survival and Function via PI3K/Akt Signaling Pathways
Authors: Krishnamurthy Mansa , Li Jinming , Fellows George F. , Rosenberg Lawrence , Goodyer Cynthia G. , Wang Rennian 
Published: December 2010

Abstract
β1-Integrin is a well-established regulator of β-cell activities; however, the role of its associated α-subunits is relatively unknown. Previously, we have shown that human fetal islet and INS-1 cells highly express α3β1-integrin and that collagens I and IV significantly enhance their survival and function; in addition, blocking β1 function in the fetal islet cells decreased adhesion on collagen I and increased apoptosis. The present study investigates the effect of blocking α3. Using α3 blocking antibody or small interfering RNA, the effects of α3-integrin blockade were examined in isolated human fetal or adult islet cells or INS-1 cells, cultured on collagens I or IV. In parallel, β1 blockade was analyzed in INS-1 cells. Perturbing α3 function in human islet or INS-1 cells resulted in significant decreases in cell function (adhesion, spreading, proliferation and Pdx1 and insulin expression/secretion), primarily on collagen IV. A significant decrease in focal adhesion kinase and ERK1/2 phosphorylation and increased caspase3 cleavage were observed on both collagens. These effects were similar to changes after β1 blockade. Interestingly, only α3 blockade reduced expression of phospho-Akt and members of its downstream signaling cascades (glycogen synthase kinase β and X-linked inhibitor of apoptosis), demonstrating a specific effect of α3 on the phosphatidylinositol 3-kinase/Akt pathway. These results suggest that α3- as well as β1-integrin-extracellular matrix interactions are critical for modulating β-cell survival and function through specialized signaling cascades and enhance our understanding of how to improve islet microenvironments for cell-based treatments of diabetes.
Nebivolol Attenuates Redox-Sensitive Glomerular and Tubular Mediated Proteinuria in Obese Rats
Authors: Habibi Javad , Hayden Melvin R. , Sowers James R. , Pulakat Lakshmi , Tilmon Roger D. , Manrique Camila , Lastra Guido , DeMarco Vincent G. , Whaley-Connell Adam 
Published: December 2010

Abstract
Obesity and insulin resistance-related proteinuria is associated with oxidative stress and impaired tissue bioavailable nitric oxide. Recent data suggest that nicotinamide adenine dinucleotide phosphate oxidase-mediated oxidative injury to the proximal tubule, like that seen in the glomerulus, contributes to proteinuria in insulin-resistant states. The vasodilator β-blocker nebivolol reduces nicotinamide adenine dinucleotide phosphate oxidase activity, increases bioavailable nitric oxide, and improves insulin sensitivity. To test the hypothesis that a treatment strategy that reduces oxidative stress and attenuates obesity-associated increases in glomerular and proximal tubule derived protein, we treated young Zucker obese (ZO) and age-matched Zucker lean male rats with nebivolol (10 mg · kg−1 · d−1) for 21 d. Compared with Zucker lean, ZO controls exhibited increased proteinuria and γ-glutamyl transpeptidase, reductions in systemic insulin sensitivity in association with increased renal renin, (pro)renin receptor, angiotensin II type 1 receptor, and mineralocorticoid receptor immunostaining, oxidative stress, and glomerular tubular structural abnormalities that were substantially improved with in vivo nebivolol treatment. Nebivolol treatment also led to improvements in glomerular podocyte foot-process effacement and improvement in podocyte-specific proteins (nephrin and synaptopodin) as well as proximal tubule-specific proteins (megalin and lysosomal-associated membrane protein-2) and proximal tubule ultrastructural remodeling in the ZO kidney. Our findings support the notion that obesity and insulin resistance lead to increased glomerulotubular oxidative stress and resultant glomerular and tubular sources of excess urine protein. Furthermore, the results of this study suggest the beneficial effect of nebivolol on proteinuria was derived from improvements in weight and insulin sensitivity and reductions in renal oxidative stress in a state of obesity and insulin resistance.
Is the Vitamin D Receptor Found in Muscle?
Authors: Wang Yongji , DeLuca Hector F. 
Published: December 2010

AbstractThe active form of vitamin D, 1α,25-dihydroxyvitamin D3, is critical for the regulation of serum calcium and phosphorus levels that in turn support bone mineralization and neuromuscular activity. It is well known that vitamin D deficiency causes rachitic/osteomalacic myopathy and cardiac disorder and the provision of vitamin D can reverse the symptoms. However, the underlying mechanisms remain unclear. The question of whether the vitamin D receptor is found in muscle has been debated but not settled. We recently studied all available antibodies against the vitamin D receptor and found that most antibodies used detect proteins other than the vitamin D receptor, and therefore, the utility of these antibodies may generate the false-positive results. Using antibodies that do not detect proteins in tissues from vitamin D receptor null mice, we have developed a specific and sensitive immunohistochemical assay. The results from this investigation show that the vitamin D receptor is undetectable in skeletal, cardiac, and smooth muscle, suggesting that the function of vitamin D on muscle is either of an indirect nature or does not involve the known receptor.
Prognostic Factors of Disease-Free Survival after Thyroidectomy in 170 Young Patients with a RET Germline Mutation: A Multicenter Study of the Groupe Français d'Etude des Tumeurs Endocrines
Authors: Rohmer V. , Vidal-Trecan G. , Bourdelot A. , Niccoli P. , Murat A. , Wemeau J. L. , Borson-Chazot F. , Schvartz C. , Tabarin A. , Chabre O. , Chabrier G. , Caron P. , Rodien P. , Schlumberger M. , Baudin E. ,   for the Groupe Français des Tumeurs Endocrines
Published: December 2010

Background:
In hereditary medullary thyroid carcinoma (HMTC), prophylactic surgery is the only curative option, which should be properly defined both in time and extent.

Objectives:
To identify and characterize prognostic factors associated with disease-free survival (DFS) in children from HMTC families.

Design:
We conducted a retrospective analysis of a multi-center cohort of 170 patients below age 21 at surgery. Demographic, clinical, genetic, biological data [basal and pentagastrine-stimulated calcitonin (CT and CT/Pg, respectively)], and tumor node metastasis (TNM) status were collected. DFS was assessed based on basal CT levels. Kaplan–Meier curves, Cox regression, and logistic regression models were used to determine factors associated with DFS and TNM staging.

Results:
No patients with a preoperative basal CT &lt;31 ng/ml had persistent or recurrent disease. Medullary thyroid carcinoma defined by a diameter ≥10 mm [hazard ratio (HR): 6.0; 95% confidence interval (95% CI): 1.8–19.8] and N1 status (HR: 20.8; 95% CI: 3.9–109.8) were independently associated with DFS. Class D genotype [odds ratio (OR): 48.5, 95% CI: 10.6–225.1], preoperative basal CT &gt;30 ng/liter (OR: 43.4, 95% CI: 5.2–359.8), and age &gt;10 (OR: 5.5, 95% CI: 1.4–21.8) were associated with medullary thyroid carcinoma ≥10 mm. No patient with a preoperative basal CT &lt;31 ng/ml had a N1 status. Class D genotype (OR: 48.6, 95% CI: 8.6–274.1), and age &gt;10 (OR: 4.6, 95% CI: 1.1–19.0) were associated with N1 status.

Conclusion:
In HMTC patients, DFS is best predicted by TNM staging and preoperative basal CT level below 30 pg/ml. Basal CT, class D genotype, and age constitute key determinants to decide preoperatively timely surgery.
Metformin Treatment Exerts Antiinvasive and Antimetastatic Effects in Human Endometrial Carcinoma Cells
Authors: Tan Bee K. , Adya Raghu , Chen Jing , Lehnert Hendrik , Cassia Louis J. Sant , Randeva Harpal S. 
Published: December 2010

Context:
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women associated with an increased risk of endometrial hyperplasia. We sought to study the effects of metformin treatment (widely used in the management of PCOS women) on human endometrial adenocarcinoma cells.

Objectives:
To study the effects of metformin treatment on in vitro invasion and metastasis in human endometrial adenocarcinoma cells. Also, given the link between inflammation with endometrial cancer invasion and metastasis, we explored the roles of nuclear factor-κB (NF-κB), matrix metalloproteinases (MMPs) as well as v-akt murine thymoma viral oncogene homolog 1 (Akt) and extracellular signal-regulated kinases (Erk1/2) signaling pathways.

Design:
Sera were obtained from PCOS and control subjects. In vitro invasion were assessed in human endometrial cells (ECC-1 cells) by wound-healing motility and migration assays. NF-κB was studied by stably transfecting ECC-1 cells with a cis-reporter plasmid containing luciferase reporter gene linked to five repeats of NF-κB binding sites. The gelatinolytic activities of secreted MMP-2/9 in conditioned media were measured by gelatin zymography. Akt and Erk1/2 phosphorylation were assessed by Western blotting.

Results:
In vitro invasion in ECC-1 cells was significantly attenuated by sera from PCOS women after 6 months of metformin treatment (850 mg twice daily) compared to matched controls (P &lt; 0.01). These effects appear to be associated with NF-κB, MMP-2/9, as well as Akt and Erk1/2 pathways that are known to be important regulators of inflammation, tumor invasion and metastasis.

Conclusions:
Metformin, potentially, may serve as adjuvant treatment in the management of patients with endometrial cancer.
Dentists’ and Specialists’ Knowledge of Chronic Orofacial Pain: Results from a Continuing Professional Development Survey
Authors: Aggarwal Vishal R , Joughin Amy , Zakrzewska Joanna M , Crawford Fiona J , Tickle Martin 
Published: December 2010

Aim To explore the knowledge of chronic orofacial pain within general dental practitioners (GDPs) and dental specialists. Methods Following a recent national survey of GDPs and specialists on the diagnosis of facial pain, all those who responded were asked to answer four multiple-choice questions on chronic orofacial pain as part of a continuing professional development exercise. The questions were formulated using a review of the literature and consultation with a facial pain expert and were administered by post. Results Of the 380 subjects who completed the original survey, 212 (56%) returned completed multiple-choice questionnaires. Specialists correctly answered significantly more questions than GDPs ( P<0.001). The majority of specialists—49/83 (59%)—obtained a score of three or more, compared to 39/129 (30%) GDPs. This was due to variation in answering one question. Significantly more specialists—50 (60%)—correctly selected trigeminal neuralgia (TN) as a condition that is not associated with COFP, whereas only 41 (32%) GDPs chose this answer. Both specialists and GDPs grossly underestimated the prevalence of COFP in secondary care clinics. Conclusions The results suggest that specialists and GDPs may have sufficient knowledge to make an appropriate diagnosis of COFP, but they also highlight the knowledge gaps and perhaps the need for more extensive inclusion of COFP in the dental undergraduate curriculum.
Age-related macular degeneration: genetic and clinical findings
Authors: Kokotas Haris , Grigoriadou Maria , Petersen Michael B. 
Published: December 2010

Abstract
Age-related macular degeneration (AMD) is a sight threatening eye disease that affects millions of humans over the age of 65 years. It is considered to be the major cause of irreversible blindness in the elderly population in the developed world. The disease is prevalent in Europe and the United States, which has a large number of individuals of European descent. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes that occur in the interface between the neural retina and the underlying choroid. This location contains the retinal photoreceptors, the retinal pigmented epithelium, a basement membrane complex known as Bruch’s membrane and a network of choroidal capillaries. AMD is increasingly recognized as a complex genetic disorder where one or more genes contribute to an individual’s susceptibility to development of the condition, while the prevailing view is that the disease stems from the interaction of multiple genetic and environmental factors. Although it has been proposed that a threshold event occurs during normal aging, the sequelae of biochemical, cellular, and molecular events leading to AMD are not fully understood. Here, we review the clinical aspects of AMD and summarize the genes which have been reported to have a positive association with the disease.
Response Behavior of Asphalt Mixtures at Low Temperatures Under Varying Indirect Tensile Test Loading Conditions
Authors: Li Xinjun , Marasteanu Mihai O. , Labuz Joseph F. , Williams R. Christopher 
Published: December 2010

Abstract
This paper investigates the effect of loading level and loading rate on the damage development and strength of asphalt mixtures. Indirect tensile creep tests with different loading levels and strength tests with three loading rates were performed at three low temperatures for ten mixtures. An acoustic emission (AE) system with eight recording channels was used to monitor the development of micro cracking in the specimens for both tests for one mixture. The experimental results show that test temperature has a significant effect on the behavior of the material. Data analysis from the creep test indicates that the creep loading level significantly affects the response of the tested material. The AE rate analysis shows that no actual damage develops when a creep load is less than 20 % of the strength and significant micro damage accumulates when the applied creep load is more than 30 % of the strength value. The loading rate was found to have a significant effect on the measured tensile strength even at a relatively low temperature, and the measured tensile strength increases with the increase of the loading rate for all the test temperatures considered in this study. However, this effect was found to be diluted with the decrease of the test temperature. The AE analysis indicates that a damage zone develops in both the creep and strength tests. The damage zone decreases with temperature decrease and increases with the increase of the loading level applied during the creep test. The damage zone obtained from the strength test was approximately equal to that from the creep testing with a loading level about 25–50 % of the strength value.
Effectiveness of a Hypertension Care Management Program Provided by Clinical Pharmacists for Veterans
Authors: Bex Susan D. , Boldt Amy S. , Needham Sarah B. , Bolf Stacy M. , Walston Cassandra M. , Ramsey Darin C. , Schmelz Andrew N. , Zillich Alan J. 
Published: December 2010

Study Objective. To evaluate the effectiveness of a hypertension care management program provided by clinical pharmacists.Design. Pre‐ and postintervention design with retrospective medical record review.Setting. Tertiary care Veterans Affairs medical center and affiliated primary care clinics.Patients. Five hundred seventy‐three veterans with hypertension who were referred to the program between June 1, 2007, and May 31, 2008.Intervention. Participation in the hypertension care management program provided by clinical pharmacists who met individually with patients, orchestrated drug therapy, and provided patient counseling.Measurements and Main Results. The following data were collected from patients' medical records: demographics, date of program referral, dates of pharmacist visits, blood pressure at each visit, concurrent antihypertensive drugs and their dosages, drug changesat each visit, as wellas patient education topics discussed during a visit. To ensure a minimum of 6 months of follow‐up data for all patients, data collection continued through November 30, 2008, for a total study duration of 18 months. The primary study outcome was the difference between systolic and diastolic blood pressure measurements at the final pharmacist care management visit and those measurements at the initial pharmacist visit. Systolic blood pressure decreased from a mean ± SD of 141.3 ± 18.5 mm Hg at the initial pharmacist visit to 130.1 ± 13.8 mm Hg at the final pharmacist visit, and diastolic blood pressure decreased from 79.1 ± 12.2 to 74.5 ± 10.3 mm Hg (p<0.001 for both comparisons). The secondary outcome was the proportion of patients reaching blood pressure treatment goals at the final visit compared with the initial pharmacist visit. Of the 573 patients, 431 (75.2%) reached blood pressure treatment goals at the final visit (p≤0.001) compared with 221 (38.6%) at the initial visit. The study patients had several comorbid diseases, including diabetes mellitus (196 patients [34.2%]) and chronic kidney disease (43 patients [7.5%]). Both study outcomes were also assessed for these subgroups.Conclusion. Patients referred to the hypertension care management program had a significant reduction in blood pressure, and most met their blood pressure treatment goals. This pharmacist‐managed program may be an efficient method of care delivery to improve patient outcomes.
The Soft Power of Solid Medicine
Authors: Donahue Donald A , Cunnion Stepen O , Brocker Fred L , Carmona Richard H 
Published: December 2010

AbstractMedical assistance undertakings have a long history of engendering positive international relations and fostering domestic stability. Interactions ranging from military medical civic action program (MEDCAP) missions to nongovernmental organization (NGO) efforts have demonstrated effectiveness, yet this capability is not routinely available in a meaningful way to the Secretary of State or the extended diplomatic community. MEDCAP and other global military presences can generate positive reactions, but can also be tainted by host nation suspicions of ulterior motives. In this paper, the authors posit that an organized, global public health presence would support international diplomacy while also establishing a worldwide surveillance capability for emerging communicable diseases.
Aging Research: Translating Scientific Discovery into Clinical Intervention
Authors: Hodes Richard J , Cahan Vicky , Homer Megan J 
Published: December 2010

AbstractThe world population is aging, and at a steadily increasing rate. In many ways people are not only living longer, but healthier. However, the challenges of an aging population, for individuals and society, are also increasingly evident: a significant percentage of older Americans report functional problems, rates of morbidity from heart disease and hypertension are still high, and exponential growth in Alzheimer's disease is predicted without new and more effective treatments. This article highlights some of the National Institute on Aging's research, including basic studies in genetics and the biological determinants of aging, translational studies in Alzheimer's disease, studies to reduce disease and disability among older adults, and studies of the social and behavioral aspects of aging and Comparative Effectiveness Research (CER). The revolution in longevity brings with it an increased urgency to understand aging. A broad‐based effort across key areas—basic biology, epidemiology, translational and clinical medicine, and social and behavioral factors—is critical to discovering new ways to support better health and maintain independence for older people.