bluuebunny/crossref_metadata_2025 huggingface dataset:
MLK3 Regulates Paxillin Phosphorylation in Chemokine-Mediated Breast Cancer Cell Migration and Invasion to Drive Metastasis
Authors: Chen Jian , Gallo Kathleen A.
Published: June 2012

MLK3 kinase activates multiple mitogen-activated protein kinases and plays a critical role in cancer cell migration and invasion. In the tumor microenvironment, prometastatic factors drive breast cancer invasion and metastasis, but their associated signaling pathways are not well-known. Here, we provide evidence that MLK3 is required for chemokine (CXCL12)-induced invasion of basal breast cancer cells. We found that MLK3 induced robust phosphorylation of the focal adhesion scaffold paxillin on Ser 178 and Tyr 118, which was blocked by silencing or inhibition of MLK3-JNK. Silencing or inhibition of MLK3, inhibition of JNK, or expression of paxillin S178A all led to enhanced Rho activity, indicating that the MLK3–JNK–paxillin axis limits Rho activity to promote focal adhesion turnover and migration. Consistent with this, MLK3 silencing increased focal adhesions and stress fibers in breast cancer cells. MLK3 silencing also decreased the formation of breast cancer lung metastases in vivo, and breast cancer cells derived from mouse lung metastases showed enhanced Ser 178 paxillin phosphorylation. Taken together, our findings suggest that the MLK3–JNK–paxillin signaling axis may represent a potential therapeutic target and/or prognostic marker in breast cancer metastasis. Cancer Res; 72(16); 4130–40. ©2012 AACR.
ERG Rearrangement for Predicting Subsequent Cancer Diagnosis in High-Grade Prostatic Intraepithelial Neoplasia and Lymph Node Metastasis
Authors: Gao Xin , Li Liao-Yuan , Zhou Fang-Jian , Xie Ke-Ji , Shao Chun-Kui , Su Zu-Lan , Sun Qi-Peng , Chen Ming-Kun , Pang Jun , Zhou Xiang-Fu , Qiu Jian-Guang , Wen Xing-Qiao , Yang Ming , Bai Xian-Zhong , Zhang Hao , Ling Li , Chen Zhong
Published: June 2012

Purpose: We aimed to analyze whether ERG rearrangement in biopsies could be used to assess subsequent cancer diagnosis in high-grade prostatic intraepithelial neoplasia (HGPIN) and the risk of lymph node metastasis in early prostate cancer.

Experimental Design: Samples from 523 patients (361 with early prostate cancer and 162 with HGPIN) were collected prospectively. On the basis of the cutoff value established previously, the 162 patients with HGPIN were stratified to two groups: one with an ERG rearrangements rate ≥1.6% (n = 59) and the other with an ERG rearrangements rate <1.6% (n = 103). For the 361 prostate cancer cases undergoing radical prostatectomy, 143 had pelvic lymph node dissection (node-positive, n = 56 and node-negative, n = 87). All ERG rearrangement FISH data were validated with ERG immunohistochemistry.

Results: A total of 56 (of 59, 94.9%) HGPIN cases with an ERG rearrangements rate ≥1.6% and 5 (of 103, 4.9%) HGPIN cases with an ERG rearrangements rate <1.6% were diagnosed with prostate cancer during repeat biopsy follow-ups (P < 0.001). There were significant differences in ERG rearrangement rates between lymph node–positive and -negative prostate cancer (P < 0.001). The optimal cutoff value to predict lymph node metastasis by ERG rearrangement was established, being 2.6% with a sensitivity at 80.4% [95% confidence interval (CI), 67.6–89.8] and a specificity at 85.1% (95% CI, 75.8–91.8). ERG protein expression by immunohistochemistry was highly concordant with ERG rearrangement by FISH.

Conclusions: The presence of ERG rearrangement in HGPIN lesions detected on initial biopsy warrants repeat biopsies and measuring ERG rearrangement could be used for assessing the risk of lymph node metastasis in early prostate cancer. Clin Cancer Res; 18(15); 4163–72. ©2012 AACR.
New Strategies in the Treatment of Mantle Cell Lymphoma
Authors: Deng Changchun , Lee Sangmin , O'Connor Owen A.
Published: June 2012

Mantle cell lymphoma (MCL) is a rare type of non-Hodgkin lymphoma that traditionally has been thought to possess the poor-risk features of both indolent lymphoma, with its incurability, and aggressive lymphoma, with its ability to proliferate rapidly. Although there is considerable debate as to whether MCL can be cured, a number of retrospective studies are beginning to suggest an improvement in overall survival over the past decade, likely coinciding with the introduction of rituximab, more intensive chemotherapy, and the increasing use of autologous stem cell transplant (ASCT) in first remission. At present, intensive induction chemotherapy regimens consistently produce a response rate of >90%, sometimes even 100% in the first-line setting, and consolidation with ASCT in first remission can improve the complete response rate to 90%. The emergence of a more sophisticated understanding of the underlying pathogenesis, coupled with a host of new agents and targets, has again created new opportunities to improve the care of our patients with MCL. Here, we discuss many of these developments and how they may potentially affect the natural history of this disease. Clin Cancer Res; 18(13); 3499–508. ©2012 AACR.
Galectin-1 Promotes Lung Cancer Progression and Chemoresistance by Upregulating p38 MAPK, ERK, and Cyclooxygenase-2
Authors: Chung Ling-Yen , Tang Shye-Jye , Sun Guang-Huan , Chou Teh-Ying , Yeh Tien-Shun , Yu Sung-Liang , Sun Kuang-Hui
Published: June 2012

Purpose: This study is aimed at investigating the role and novel molecular mechanisms of galectin-1 in lung cancer progression.

Experimental Design: The role of galectin-1 in lung cancer progression was evaluated both in vitro and in vivo by short hairpin RNA (shRNA)-mediated knockdown of galectin-1 in lung adenocarcinoma cell lines. To explore novel molecular mechanisms underlying galectin-1–mediated tumor progression, we analyzed gene expression profiles and signaling pathways using reverse transcription PCR and Western blotting. A tissue microarray containing samples from patients with lung cancer was used to examine the expression of galectin-1 in lung cancer.

Results: We found overexpression of galectin-1 in non–small cell lung cancer (NSCLC) cell lines. Suppression of endogenous galectin-1 in lung adenocarcinoma resulted in reduction of the cell migration, invasion, and anchorage-independent growth in vitro and tumor growth in mice. In particular, COX-2 was downregulated in galectin-1–knockdown cells. The decreased tumor invasion and anchorage-independent growth abilities were rescued after reexpression of COX-2 in galectin-1–knockdown cells. Furthermore, we found that TGF-β1 promoted COX-2 expression through galectin-1 interaction with Ras and subsequent activation of p38 mitogen-activated protein kinase (MAPK), extracellular signal–regulated kinase (ERK), and NF-κB pathway. Galectin-1 knockdown sensitized lung cancer cells to platinum-based chemotherapy (cisplatin). In addition, galectin-1 and COX-2 expression was correlated with the progression of lung adenocarcinoma, and high clinical relevance of both proteins was evidenced (n = 47).

Conclusions: p38 MAPK, ERK, and COX-2 activation are novel mediators for the galectin-1–promoted tumor progression and chemoresistance in lung cancer. Galectin-1 may be an innovative target for combined modality therapy for lung cancer. Clin Cancer Res; 18(15); 4037–47. ©2012 AACR.
EZH2-Regulated DAB2IP Is a Medulloblastoma Tumor Suppressor and a Positive Marker for Survival
Authors: Smits Michiel , van Rijn Sjoerd , Hulleman Esther , Biesmans Dennis , van Vuurden Dannis G. , Kool Marcel , Haberler Christine , Aronica Eleonora , Vandertop W. Peter , Noske David P. , Würdinger Thomas
Published: June 2012

Purpose: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements, the molecular mechanisms driving medulloblastoma are not fully understood and further elucidation could provide cues to improve outcome prediction and therapeutic approaches.

Experimental Design: Here, we conducted a meta-analysis of mouse and human medulloblastoma gene expression data sets, to identify potential medulloblastoma tumor suppressor genes.

Results: We identified DAB2IP, a member of the RAS-GTPase–activating protein family (RAS GAP), and showed that DAB2IP expression is repressed in medulloblastoma by EZH2-induced trimethylation. Moreover, we observed that reduced DAB2IP expression correlates significantly with a poor overall survival of patients with medulloblastoma, independent of metastatic stage. Finally, we showed that ectopic DAB2IP expression enhances stress-induced apoptosis in medulloblastoma cells and that reduced expression of DAB2IP in medulloblastoma cells conveys resistance to irradiation-induced cell death.

Conclusion: These results suggest that repression of DAB2IP may at least partly protect medulloblastoma cells from apoptotic cell death. Moreover, DAB2IP may represent a molecular marker to distinguish patients with medulloblastoma at high risk from those with a longer survival prognosis. Clin Cancer Res; 18(15); 4048–58. ©2012 AACR.
A 2-Stage Phase II Design with Direct Assignment Option in Stage II for Initial Marker Validation
Authors: An Ming-Wen , Mandrekar Sumithra J. , Sargent Daniel J.
Published: June 2012

Biomarkers are critical to targeted therapies, as they may identify patients more likely to benefit from a treatment. Several prospective designs for biomarker-directed therapy have been previously proposed, differing primarily in the study population, randomization scheme, or both. Recognizing the need for randomization, yet acknowledging the possibility of promising but inconclusive results after a stage I cohort of randomized patients, we propose a 2-stage phase II design on marker-positive patients that allows for direct assignment in a stage II cohort. In stage I, marker-positive patients are equally randomized to receive experimental treatment or control. Stage II has the option to adopt “direct assignment” whereby all patients receive experimental treatment. Through simulation, we studied the power and type I error rate of our design compared with a balanced randomized two-stage design, and conducted sensitivity analyses to study the effect of timing of stage I analysis, population shift effects, and unbalanced randomization. Our proposed design has minimal loss in power (<1.8%) and increased type I error rate (<2.1%) compared with a balanced randomized design. The maximum increase in type I error rate in the presence of a population shift was between 3.1% and 5%, and the loss in power across possible timings of stage I analysis was less than 1.2%. Our proposed design has desirable statistical properties with potential appeal in practice. The direct assignment option, if adopted, provides for an “extended confirmation phase” as an alternative to stopping the trial early for evidence of efficacy in stage I. Clin Cancer Res; 18(16); 4225–33. ©2012 AACR.
Effect of Subthalamic Nucleus Deep Brain Stimulation on the Autonomic Nervous System in Parkinson’s Disease Patients Assessed by Spectral Analyses of R-R Interval Variability and Blood Pressure Variability
Authors: Sumi Koichiro , Katayama Yoichi , Otaka Toshiharu , Obuchi Toshiki , Kano Toshikazu , Kobayashi Kazutaka , Oshima Hideki , Fukaya Chikashi , Yamamoto Takamitsu , Ogawa Yojiro , Iwasaki Kenichi
Published: June 2012

Objective: Autonomic nervous system impairment is an untoward symptom that is typically observed in advanced Parkinson’s disease (PD) patients. However, details of the effects of subthalamic nucleus deep brain stimulation (STN-DBS) on the autonomic nervous system remain unclear. Methods: Twenty-eight patients with advanced PD (12 males and 16 females) who underwent bilateral STN-DBS and 13 age-matched healthy controls were included in this study. We analyzed the dynamic cardiovascular autonomic function regulating the R-R interval and blood pressure by spectral and transfer function analyses of cardiovascular variability before and after STN-DBS. Results: Vagally mediated arterial-cardiac baroreflex function improved after STN-DBS compared to that before STN-DBS (p < 0.05). However, there were no statistically significant differences in the results of the comparison of vagally mediated arterial-cardiac baroreflex function between on-stimulation and off-stimulation. Conclusions: The vagal component in cardiac autonomic dysfunction associated with PD is expected to improve after STN-DBS. We considered that the patients improved their lifestyle; in particular, increasing the amount of exercise by STN-DBS and the best pharmachological treatment may have positive effects on parasympathetic activities.
Clinical Profiles, Endoscopic and Laboratory Features and Associated Factors in Patients with Autoimmune Gastritis
Authors: Soykan Irfan , Yakut Mustafa , Keskin Onur , Bektaş Mehmet
Published: June 2012

Background/Aims: Autoimmune gastritis (AIG) may predispose to gastric carcinoid tumors or adenocarcinomas and may also cause unexplained iron and/or vitamin B12 deficiency. The aims of this study were to explore clinical manifestations, endoscopic findings and laboratory features of patients with AIG. Methods: 109 patients with AIG were enrolled into the study. In addition to demographic and clinical data, gastric lesions, serum gastrin, vitamin B12, antiparietal cell antibody (APA), current Helicobacter pylori status, and anti-H. pylori IgG were also investigated. Results: The mean age of the patients was 53.06 ± 12.7 years (range 24–81; 72 (66.1%) women). The most common main presenting symptom was abdominal symptoms in 51 patients, consultation for iron and/or vitamin B12 deficiency in 36, and non-specific symptoms including intermittent diarrhea in 15 patients. Endoscopic lesions were detected in 17 patients, hyperplastic polyps in 8, gastric carcinoid tumor in 4, fundic gland polyps in 3, and adenomatous polyps in 2 patients. H. pylori was negative in all patients in biopsy specimens; however, anti-H. pylori IgG was positive in 30 (27.5%) patients. 91 patients (83.4%) were positive for APA. Conclusion: In patients with AIG, the main symptoms prompted for clinical investigation were: abdominal symptoms, iron/B12 deficiency and non-specific symptoms. 20% of patients with AIG had various gastric lesions including type I gastric carcinoids. None of the patients were positive for H. pylori by means of invasive tests; however, anti-H. pylori IgG was found in 27.5% of patients. Patients referring with non-specific abdominal symptoms such as bloating, diarrhea and iron/B12 deficiency should be investigated for the presence of AIG.
Stroke in Renaissance Time: The Case of Francesco I de’ Medici
Authors: Arba Francesco , Inzitari Domenico , Barnett Henry Joseph Macaulay , Lippi Donatella
Published: June 2012

Francesco I de’ Medici (1541–1587), the second Grand Duke of Tuscany, was one of the members of the Medici family who ruled Florence during the centuries of the Renaissance. When, in 1857, all members of the Medici family were exhumed and definitively buried in the place where they still lie buried today, a painter, Giuseppe Moricci (Florence 1806–1879), who attended the ceremony, depicted the corpse of Francesco I in a perfect state of preservation. The painting shows a right spastic hemiparesis with a facial droop, a claw-hand appearance, the right shoulder internally rotated, the calf muscle wasted and the clubfoot confirmed by an orthopedic footwear in the coffin. The hemiparesis and consequent disability were likely concealed when Francesco I was alive, since in official portraits the Grand Duke appeared in perfect physical condition. However, chronicles reported that he had suffered from malaria and syphilis. Later in his life, temper and behavioral changes as well as emotional instability were documented, together with handwriting deterioration and seizures. We postulate that Francesco I had suffered from a stroke consequent to syphilis, a new aggressive and rapidly spreading infectious disease at that time in Italy. Francesco’s governmental skills were presumably altered due to these diseases. Disability consequent to stroke was likely concealed by official portrayers and biographers of Francesco I during his life, consistent with the King’s two bodies theory common since the Middle Ages: while the King’s physical body is destined to die, the political one is everlasting. Infectious diseases have remained a leading cause of stroke in underdeveloped countries until recently, but noncommunicable causes are now prevailing worldwide.
Implementing On-Line Hemodiafiltration as a Renal Replacement Therapy for ICU Acute Renal Failure: A Single-Center Report of Feasibility, Safety and Hemodynamic Tolerance over a Seven-Year Period
Authors: Klouche Kada , Amigues Laurent , Serveaux-Delous Marianne , Machado Sonia , Delabre Jean-Philippe , Laydet Erick , Mauran Philippe , Jonquet Olivier , Canaud Bernard
Published: June 2012

Background/Aims: On-line hemodiafiltration (HDF) is not yet routinely used in ICUs given the potential risk of microbial contamination of dialysis fluids. We evaluated the safety and the tolerance of its use in our ICU. Methods: A weekly measurement of bacterial growth (CFU/ml) and endotoxin level (endotoxin units/ml) was performed in dialysis fluids over a 7-year period. Intradialytic hypotensive events and pyrogenic reactions were collected during 466 on-line HDF sessions. Results: A bacterial count <0.1 CFU/ml was achieved in 977/978, 288/290, and 278/280, and an endotoxin level <0.03 endotoxin units/ml in 564/576, 330/337 and 318/323 ultrapure water, dialysate, and infusate samples, respectively. Seventy-six intradialytic hypotensive events but no pyrogenic reaction occurred. Conclusion: The great majority of dialysis fluid samples were considered suitable with a 99% compliance rate. Use of on-line HDF, at a large scale of dialysate and infusate flows, is well tolerated and may be safely performed in critically ill.
Review and Recommendations for Zero-Inflated Count Regression Modeling of Dental Caries Indices in Epidemiological Studies
Authors: Preisser J.S. , Stamm J.W. , Long D.L. , Kincade M.E.
Published: June 2012

Over the past 5–10 years, zero-inflated (ZI) count regression models have been increasingly applied to the analysis of dental caries indices (e.g. DMFT, dfms). The main reason for that is linked to the broad decline in children’s caries experience, such that dmf and DMF indices more frequently generate low or even zero counts. This article specifically reviews the application of ZI Poisson and ZI negative binomial regression models to dental caries, with emphasis on the description of the models and the interpretation of fitted model results given the study goals. The review finds that interpretations provided in the published caries research are often imprecise or inadvertently misleading, particularly with respect to failing to discriminate between inference for the class of susceptible persons defined by such models and inference for the sampled population in terms of overall exposure effects. Recommendations are provided to enhance the use as well as the interpretation and reporting of results of count regression models when applied to epidemiological studies of dental caries.
A Comparison of Herpes Zoster Incidence across the Spectrum of Chronic Kidney Disease, Dialysis and Transplantation
Authors: Lin Shih-Yi , Liu Jiung-Hsiun , Lin Cheng-Li , Tsai I-Ju , Chen Pei-Chun , Chung Chi-Jung , Liu Yao-Lung , Wang I-Kuan , Lin Hsin-Hung , Huang Chiu-Ching
Published: June 2012

Background: The effect of different renal replacement therapies on the risk of developing herpes zoster in renal failure patients is unknown. We aimed to investigate the incidence of herpes zoster attack among renal failure patients who were receiving different dialysis modalities, renal transplantation (RT), or not receiving any of the above mentioned therapies yet. Methods: A retrospective cohort study of the national health insurance register database was conducted. This observational cohort study involved 79,581 study controls, 15,802 chronic kidney disease patients, 3,694 hemodialysis (HD) patients, 317 peritoneal dialysis (PD) patients, and 159 RT patients. Results: The RT group had the worst risk of herpes zoster (hazard ratio, HR, 8.46; 95% CI 5.85–12.2), followed by PD (HR 3.61; 95% CI 2.49–4.83) and HD (HR 1.35; 95% CI 1.18–1.55), compared with the comparison group (p < 0.0001). The RT group had also the highest risk of developing herpes zoster with complications among all groups (adjusted HR 15.3). The HRs of the PD group were higher than the HRs of the HD group in terms of herpes zoster or its complications (p < 0.0001 and p = 0.0002, respectively). Conclusions: This study suggests that different treatment modalities are associated with different risks of herpes zoster attacks in renal failure patients. PD patients had higher risks than the HD group in terms of herpes zoster or its complications.
Renal Function Trajectory Is More Important than Chronic Kidney Disease Stage for Managing Patients with Chronic Kidney Disease
Authors: Rosansky Steven J.
Published: June 2012

Management of patients with chronic kidney disease (CKD) emphasizes a current level of function as calculated from the modification of diet in renal disease glomerulofiltration rate equations (eGFR) and proteinuria for staging of CKD. Change in a patient’s eGFR over time (renal function trajectory) is an additional and potentially more important consideration in deciding which patients will progress to the point where they will require renal replacement therapy (RRT). Many patients with CKD 3–5 have stable renal function for years. Proteinuria/albuminuria is a primary determinant of renal trajectory which may be slowed by medications that decrease proteinuria and/or aggressively lower blood pressure. A renal trajectory of >3 ml/min/1.73 m2/year may relate to a need for closer renal follow-up and increased morbidity and mortality. Additional CKD population-based studies need to examine the relationship of renal trajectory to: baseline renal function; acute kidney injury episodes; age, race, sex and primary etiologies of renal disease; blood pressure control and therapies; dietary protein intake; blood glucose control in diabetics and the competitive risk of death versus the requirement for renal replacement therapy. In the elderly CKD 4 population with significant comorbidities and slow decline in renal function, the likelihood of death prior to the need for RRT should be considered before placing AV access for dialysis. Prediction models of renal progression must account for the competitive risk of death as well as stable or improved renal function to be clinically useful.
Influence of Creatinine versus Glomerular Filtration Rate on Non-Steroidal Anti-Inflammatory Drug Prescriptions in Chronic Kidney Disease
Authors: Patel Krupa , Diamantidis Clarissa , Zhan Min , Hsu Van Doren , Walker Loreen D. , Gardner James , Weir Matthew R. , Fink Jeffrey C.
Published: June 2012

Background: Non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors, are generally contraindicated in chronic kidney disease (CKD). This investigation sought to identify the frequency of NSAID/COX-2 prescription and to determine the influence of serum creatinine (Cr) versus estimated glomerular filtration rate (eGFR) on this practice pattern. Methods: An established Veterans Health Administration CKD safety cohort (n = 70,154) was examined to determine the frequency of NSAID/COX-2 in fiscal year 2005 (FY05) for up to 30 days preceding the index hospitalization and as many as 365 days during that year. Binomial regression was used to determine adjusted prevalence ratios for prescription of NSAID/COX-2 with respect to continuous eGFR measurement and serum Cr categories. CKD was defined as eGFR <60 ml/min/1.73 m2. Results: 15.4% of the subjects had an NSAID/COX-2 prescription during the observation period. The proportion of these prescribed agents decreased with declining renal function, but remained significant at any stage of CKD given the renal harm related to these medications. At specific GFR estimates, serum Cr remained a significant predictor of NSAID/COX-2 prescription. At GFR set at 42 ml/min/1.73 m2, the predicted proportion of prescribed NSAID/COX-2 was 0.29 (95% CI 0.24, 0.36), 0.23 (95% CI 0.22, 0.26), 0.20 (95% CI 0.19, 0.22), and 0.12 (95% CI 0.10, 0.14) for Cr strata of ≤1.3, 1.4–1.6, 1.7–2.1, and ≥2.2 mg/dl, respectively (all p < 0.05). Conclusion: A significant proportion of individuals with CKD continue to be prescribed NSAID/COX-2 and serum Cr remains an influential guide to NSAID/COX-2 prescription, even in GFR ranges where these agents are ill advised.
Low Adiponectin, High Levels of Apoptosis and Increased Peripheral Blood Neutrophil Activity in Healthy Obese Subjects
Authors: Trellakis Sokratis , Rydleuskaya Alena , Fischer Cornelia , Canbay Ali , Tagay Sefik , Scherag André , Bruderek Kirsten , Schuler Patrick J. , Brandau Sven
Published: June 2012

Objective: Growing evidence supports a link between obesity and inflammation. Current research is focused on the role of adipokines such as adiponectin and immune cells, especially macrophages, in adipose tissue. Our aim was to examine the role of inflammation not in tissue but in the peripheral blood of healthy overweight and obese subjects. We especially investigated the role of neutrophils and their possible regulation by adiponectin. Methods: In healthy normal-weight, overweight, and obese human subjects (n = 32) the peripheral blood concentrations of adipokines, satiety hormones, apoptosis markers, and cytokines as well as the blood count were related to inflammation and neutrophils, at 3 independent days of examination. The response of neutrophils to stimulation by adiponectin was also investigated in vitro. Results: In obese and by tendency already in overweight subjects, inflammation was increased showing a higher neutrophil-to-lymphocyte ratio, elevated high-sensitivity C-reactive protein, increased chemokines (CXCL8, CCL3, CCL5), increased apoptosis markers (M30 and M65), and changes in hormone levels in the peripheral blood. LPS- and fMLP-induced production of CXCL8 by neutrophils was elevated in overweight and obese subjects. High plasma levels of adiponectin were associated with reduced CXCL8 production in peripheral blood neutrophils. In vitro, production of CXCL8 by neutrophils was inhibited by adiponectin. Conclusion: Reduced adiponectin and enhanced apoptosis may occur already in the peripheral blood of healthy overweight subjects. This process seems to further enhance neutrophil activity in overweight and obese.
What Are Obese Patients Able to Eat after Roux-en-Y Gastric Bypass?
Authors: Ortega Joaquin , Ortega-Evangelio Graciela , Cassinello Norberto , Sebastia Vicente
Published: June 2012

Background/Aims: The goal of this study was to analyze the likelihood of patients undergoing Roux-en-Y gastric bypass (RYGB) to recover a normal daily food intake, and the possible influence of dietary and exercise habits on long-term weight loss. Methods: The sample included 107 morbidly obese postoperative patients with at least 1 year of follow-up. The data collected included anthropometry, dietary and exercise habits, and information on ingested food. The unpaired Student’s t test and the multivariate step-by-step regression were used in the analysis. Results: The mean preoperative BMI was 50.7 ± 11.8 kg/m2, which had decreased at the moment of survey to 31.7 ± 5.4 kg/m2. The mean % Excess of BMI Lost (%EBMIL) was 77.4 ± 23.7%. The nutritional components of diet were similar to those for the nonobese population. There were no significant differences in %EBMIL regarding number of meals, social habits, components of diet, or amount of exercise. The daily mean caloric intake (1,364 ± 293 kcal) was the only parameter significantly related to the %EBMIL outcome. More than 30% of the patients had intolerance to certain foods. Conclusion: Obese patients undergoing RYGB can establish a postoperative lifestyle and diet similar to the ideal. Only the daily amount of ingested calories demonstrated a statistically significant influence on weight loss over time.
Liver-Specific Deletion of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Causes Hepatic Steatosis and Death
Authors: Nagashima Shuichi , Yagyu Hiroaki , Ohashi Ken , Tazoe Fumiko , Takahashi Manabu , Ohshiro Taichi , Bayasgalan Tumenbayar , Okada Kenta , Sekiya Motohiro , Osuga Jun-ichi , Ishibashi Shun
Published: June 2012

Objective—

3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) catalyzes the rate-limiting step in cholesterol biosynthesis and has proven to be an effective target of lipid-lowering drugs, statins. The aim of this study was to understand the role of hepatic HMGCR in vivo.

Methods and Results—

To disrupt the HMGCR gene in liver, we generated mice homozygous for a floxed HMGCR allele and heterozygous for a transgene encoding Cre recombinase under the control of the albumin promoter (liver-specific HMGCR knockout mice). Ninety-six percent of male and 71% of female mice died by 6 weeks of age, probably as a result of liver failure or hypoglycemia. At 5 weeks of age, liver-specific HMGCR knockout mice showed severe hepatic steatosis with apoptotic cells, hypercholesterolemia, and hypoglycemia. The hepatic steatosis and death were completely reversed by providing the animals with mevalonate, indicating its essential role in normal liver function. There was a modest decrease in hepatic cholesterol synthesis in liver-specific HMGCR knockout mice. Instead, they showed a robust increase in the fatty acid synthesis, independent of sterol regulatory element binding protein-1c.

Conclusion—

Hepatocyte HMGCR is essential for the survival of mice, and its abrogation elicits hepatic steatosis with jaundice and hypoglycemia.
The Status of Telestroke in the United States
Authors: Silva Gisele S. , Farrell Shawn , Shandra Emma , Viswanathan Anand , Schwamm Lee H.
Published: June 2012

Background and Purpose

Little is known about adoption or success of telestroke networks outside of published or federally funded programs. Under contract to the Health Resource Services Administration, we conducted an environmental scan of telestroke programs in the United States.

Methods

An analyst contacted all potential programs identified in comprehensive online searches, interviewed respondents, and collected response data about structural and functional components of currently operating telestroke programs.

Results

Among 97 potential programs contacted, 56 programs had confirmed telestroke activity, and 38 programs (68%) from 27 states participated. Hospital and community characteristics of nonparticipating programs were similar to those of participating ones. The top 3 clinical needs met by the telestroke were emergency department consultation (100%), patient triage (83.8%), and inpatient teleconsultation (46.0%). Telestroke programs were in operation a median of 2.44 years (interquartile range, 1.36–3.44 years); 94.6% used 2-way, real-time interactive video plus imaging, but only 44% used dedicated telemedicine consultation software. The mean number of spokes per hub increased significantly from 2007 to 2008 to 2009 (3.78 versus 7.60;
P
<0.05), and >80% of spoke sites were rural or small hospitals. Reimbursement was absent for >40% of sites. Sites rated inability to obtain physician licensure (27.77%), lack of program funds (27.77%), and lack of reimbursement (19.44%) as the most important barriers to program growth.

Conclusions

Telestroke is a widespread and growing practice model. Important barriers to expansion amenable to change relate to organizational, technical, and educational domains and external economic and regulatory forces.
A Parameterization for the Effects of Ozone on the Wave Driving Exerted by Equatorial Waves in the Stratosphere
Authors: Grogan Dustin F. P. , Nathan Terrence R. , Echols Robert S. , Cordero Eugene C.
Published: June 2012

An equatorial β-plane model of the tropical stratosphere is used to examine the effects of ozone on Kelvin, Rossby–gravity, equatorial Rossby, inertia–gravity, and smaller-scale gravity waves. The model is composed of coupled equations for wind, temperature, and ozone volume mixing ratio, which are linearized about a zonally averaged background state. Using the Wentzel–Kramers–Brillouin (WKB) formalism, equations are obtained for the vertical spatial scale, spatial damping rate, and amplitude of the waves. These equations yield an analytical expression for the ozone-modified wave driving of the zonal-mean circulation. The expression for the wave driving provides an efficient parameterization that can be implemented into models that are unable to spontaneously generate the ozone-modified, convectively coupled waves that drive the quasi-biennial and semiannual oscillations of the tropical stratosphere.

The effects of ozone on the wave driving, which are strongly modulated by the Doppler-shifted frequency, are maximized in the upper stratosphere, where ozone photochemistry and vertical ozone advection combine to augment Newtonian cooling. The ozone causes a contraction in spatial scale and an increase in the spatial damping rate. In the midstratosphere to lower mesosphere, the ozone-induced increase in wave driving is about 10%–30% for all wave types, but it can be as large as about 80% over narrow altitude regions and for specific wave types. In the dynamically controlled lower stratosphere, vertical ozone advection dominates over meridional ozone advection and opposes Newtonian cooling, causing, on average, a 10%–15% reduction in the damping rate.
Dynamical Downscaling over the Great Lakes Basin of North America Using the WRF Regional Climate Model: The Impact of the Great Lakes System on Regional Greenhouse Warming
Authors: Gula Jonathan , Peltier W. Richard
Published: June 2012

The Weather Research and Forecasting model (WRF) is employed to dynamically downscale global warming projections produced using the Community Climate System Model (CCSM). The analyses are focused on the Great Lakes Basin of North America and the climate change projections extend from the instrumental period (1979–2001) to midcentury (2050–60) at a spatial resolution of 10 km. Because WRF does not currently include a sufficiently realistic lake component, simulations are performed using lake water temperature provided by D.V. Mironov’s freshwater lake model “FLake” forced by atmospheric fields from the global simulations. Results for the instrumental era are first compared with observations to evaluate the ability of the lake model to provide accurate lake water temperature and ice cover and to analyze the skill of the regional model. It is demonstrated that the regional model, with its finer resolution and more comprehensive physics, provides significantly improved results compared to those obtained from the global model. It much more accurately captures the details of the annual cycle and spatial pattern of precipitation. In particular, much more realistic lake-induced precipitation and snowfall patterns downwind of the lakes are predicted. The midcentury projection is analyzed to determine the impact of downscaling on regional climate changes. The emphasis in this final phase of the analysis is on the impact of climate change on winter snowfall in the lee of the lakes. It is found that future changes in lake surface temperature and ice cover under warmer conditions may locally increase snowfall as a result of increased evaporation and the enhanced lake effect.
Ocean Heat Transport and Its Projected Change in CanESM2
Authors: Yang Duo , Saenko Oleg A.
Published: June 2012

The meridional ocean heat transport (MOHT), its seasonal variability, and projected changes simulated by the second generation Canadian Earth System Model (CanESM2) are presented. The global mean MOHT is within the uncertainty of the observational estimates. However, a correct simulation of the MOHT for individual ocean basins is more challenging, and the Atlantic MOHT south of 30°N is underestimated. The partitioning of the MOHT into the overturning and gyre components is generally consistent with such partitioning in an observationally optimized ocean model. At low latitudes, the time-mean MOHT is dominated by its overturning component, whereas in the Southern Ocean and, especially, in the subpolar North Atlantic, it is the gyre component that plays a more important role. In the projected warmer climates, CanESM2 simulates a weakening of the poleward MOHT essentially in both hemispheres. The projected MOHT changes are largely determined by the overturning component, except in the subpolar Atlantic where it is dominated by the gyre component. Consistent with (the limited number of) previous studies, the seasonal variability of the MOHT is large and is mostly driven by the seasonal variability of the meridional Ekman transport. In the simulated warmer climates, the seasonal cycle of the MOHT is projected to change, mostly in the tropics and also in the Southern Hemisphere midlatitudes. The eddy contribution to the MOHT is broadly consistent with that in the observationally optimized eddy-permitting model. However, in the tropics a significant fraction of the eddy energy is converted back to the mean circulation, and the heat transports due to the parameterized and permitted eddies differ.
Wildfire Management and Forecasting Fire Potential: The Roles of Climate Information and Social Networks in the Southwest United States
Authors: Owen Gigi , McLeod Jonathan D. , Kolden Crystal A. , Ferguson Daniel B. , Brown Timothy J.
Published: June 2012

Continuing progress in the fields of meteorology, climatology, and fire ecology has enabled more proactive and risk-tolerant wildland fire management practices in the United States. Recent institutional changes have also facilitated the incorporation of more advanced climate and weather research into wildland fire management. One of the most significant changes was the creation of Predictive Services in 1998, a federal interagency group composed, in part, of meteorologists who create climate- and weather-based fire outlooks tailored to fire manager needs. Despite the numerous forecast products now available to fire managers, few studies have examined how these products have affected their practices. In this paper the authors assess how fire managers in the Southwest region of the United States perceive and incorporate different types of information into their management practices. A social network analysis demonstrates that meteorologists have become central figures in disseminating information in the regional interagency fire management network. Interviews and survey data indicate that person-to-person communication during planning phases prior to the primary fire season is key to Predictive Services’ success in supporting fire managers’ decision making. Over several months leading up to the fire season, predictive forecasts based on complex climate, fuels, and fire-risk models are explained to fire managers and updated through frequent communication. The study’s findings suggest that a significant benefit of the information sharing process is the dialogue it fosters among fire managers, locally, regionally, and nationally, which better prepares them to cooperate and strategically plan for the fire season.
Numerical analysis of dielectric ceramic and void containing Ni electrode layers of multilayer ceramic capacitors
Authors: Lee Seung Pyo , Kim Jin Ho , Kim Dong Jin , Ha Sung Kyu
Published: June 2012

In this article, we performed a numerical analysis of dielectric ceramic and Ni electrode layers with voids in a multilayer ceramic capacitor using the finite element method. To numerically analyze a multilayer ceramic capacitor composed of several hundred ceramic and Ni layers, we defined a unit cell, and equivalent material properties from the ceramic and Ni layers were calculated by the homogenization method. We predicted the deformation of the overall multilayer ceramic capacitor from that of a unit cell with equivalent material properties. Voids in the Ni layer, produced during the manufacturing process, were taken into consideration. Because both ceramic and Ni layers are viscoelastic and are in contact with each other, viscoelastic and contact analyses were carried out using the commercial software ANSYS. Dynamic mechanical analysis was used to determine the viscoelastic material properties of the ceramic and Ni layers. We compared the elastic results with the viscoelastic results to determine the viscoelastic characteristics of a multilayer ceramic capacitor. The surface roughness of a multilayer ceramic capacitor was measured by confocal microscopy to verify the reliability of the numerical analysis. The experimental results showed reasonable agreement with the model-based results.
The PBRN Initiative
Authors: Curro F.A. , Vena D. , Naftolin F. , Terracio L. , Thompson V.P.
Published: June 2012

The NIDCR-supported Practice-based Research Network initiative presents dentistry with an unprecedented opportunity by providing a pathway for modifying and advancing the profession. It encourages practitioner participation in the transfer of science into practice for the improvement of patient care. PBRNs vary in infrastructure and design, and sustaining themselves in the long term may involve clinical trial validation by regulatory agencies. This paper discusses the PBRN concept in general and uses the New York University College of Dentistry’s Practitioners Engaged in Applied Research and Learning (PEARL) Network as a model to improve patient outcomes. The PEARL Network is structured to ensure generalizability of results, data integrity, and to provide an infrastructure in which scientists can address clinical practitioner research interests. PEARL evaluates new technologies, conducts comparative effectiveness research, participates in multidisciplinary clinical studies, helps evaluate alternative models of healthcare, educates and trains future clinical faculty for academic positions, expands continuing education to include “benchmarking” as a form of continuous feedback to practitioners, adds value to dental schools’ educational programs, and collaborates with the oral health care and pharmaceutical industries and medical PBRNs to advance the dental profession and further the integration of dental research and practice into contemporary healthcare (NCT00867997, NCT01268605).
The Randomized Shortened Dental Arch Study
Authors: Wolfart S. , Marré B. , Wöstmann B. , Kern M. , Mundt T. , Luthardt R.G. , Huppertz J. , Hannak W. , Reiber T. , Passia N. , Heydecke G. , Reinhardt W. , Hartmann S. , Busche E. , Mitov G. , Stark H. , Pospiech P. , Weber A. , Gernet W. , Walter M.H.
Published: June 2012

The scientific evidence concerning prosthodontic care for the shortened dental arch (SDA) is sparse. This randomized multicenter study aimed to compare two common treatment options: removable partial dental prostheses (RPDPs) for molar replacement vs. no replacement (SDA). One of the hypotheses was that the follow-up treatment differs between patients with RPDPs and patients with SDAs during the 5-year follow-up period.

Two hundred and fifteen patients with complete molar loss in one jaw were included in the study. Molars were either replaced by RPDPs or not replaced according to the SDA concept.

A mean number of 4.2 (RPDP) and 2.8 (SDA) treatments for biological or technical reasons occurred during the 5-year observation time per patient. Concerning the biological aspect, no significant differences between the groups could be shown, whereas treatment arising from technical reasons was significantly more frequent for the RPDP group. When the severity of treatment was analyzed, a change over time was evident. When, at baseline, only follow-up treatment with minimal effort is required, over time there is a continuous increase to moderate and extensive effort observed for both groups ( Controlled-trials.com number ISRCTN97265367).
Dental Abnormalities in Schimke Immuno-osseous Dysplasia
Authors: Morimoto M. , Kérourédan O. , Gendronneau M. , Shuen C. , Baradaran-Heravi A. , Asakura Y. , Basiratnia M. , Bogdanović R. , Bonneau D. , Buck A. , Charrow J. , Cochat P. , DeHaai K.A. , Fenkçi M.S. , Frange P. , Fründ S. , Fryssira H. , Keller K. , Kirmani S. , Kobelka C. , Kohler K. , Lewis D.B. , Massella L. , McLeod D.R. , Milford D.V. , Nobili F. , Olney A.H. , Semerci C.N. , Stajić N. , Stein A. , Taque S. , Zonana J. , Lücke T. , Hendson G. , Bonnaure-Mallet M. , Boerkoel C.F.
Published: June 2012

Described for the first time in 1971, Schimke immuno-osseous dysplasia (SIOD) is an autosomal-recessive multisystem disorder that is caused by bi-allelic mutations of SMARCAL1, which encodes a DNA annealing helicase. To define better the dental anomalies of SIOD, we reviewed the records from SIOD patients with identified bi-allelic SMARCAL1 mutations, and we found that 66.0% had microdontia, hypodontia, or malformed deciduous and permanent molars. Immunohistochemical analyses showed expression of SMARCAL1 in all developing teeth, raising the possibility that the malformations are cell-autonomous consequences of SMARCAL1 deficiency. We also found that stimulation of cultured skin fibroblasts from SIOD patients with the tooth morphogens WNT3A, BMP4, and TGFβ1 identified altered transcriptional responses, raising the hypothesis that the dental malformations arise in part from altered responses to developmental morphogens. To the best of our knowledge, this is the first systematic study of the dental anomalies associated with SIOD.
Oral Chronic Graft-vs.-Host Disease Characterization Using the NIH Scale
Authors: Fassil H. , Bassim C.W. , Mays J. , Edwards D. , Baird K. , Steinberg S.M. , Williams K.M. , Cowen E.W. , Mitchell S.A. , Hakim F.T. , Taylor T. , Avila D. , Zhang D. , Grkovic L. , Datiles M. , Gress R.E. , Pavletic S.Z.
Published: June 2012

Chronic graft- vs.-host disease (cGVHD) is a complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Oral cGVHD is manifested by mucosal, salivary, and/or sclerotic changes that have been linked to pain and poor quality of life. Our aim was to describe the demographic, clinical, and laboratory markers of oral cGVHD in alloHSCT patients (N = 187) enrolled in a cGVHD cross-sectional study at the NIH (#NCT00331968). We propose a meaningful and reproducible measure of disease defined by a cut-off point reflecting clinical minimally detectable change (0-2 = no oral cGVHD, 3-15 = oral cGVHD) on the 15-point NIH cGVHD clinician assessment scale. Forty-four patients had oral cGVHD. Oral cGVHD was associated with a quiescent or de novo type of cGVHD onset (p = 0.05), higher cGVHD severity (p = 0.033), lower albumin (p = 0.0008), higher total complement (p = 0.012), greater bother from foods or oral ulcers and greater mouth pain, and sensitivity (p < 0.0001). Multivariable logistic regression modeling with albumin, mouth pain, and total complement was 74.3% predictive of oral cGVHD and 80.2% predictive of non-oral cGVHD. We propose the use of >2 points on the NIH scale as a reproducible definition of clinically significant oral cGVHD, which may be useful in clinical settings or as eligibility criterion or as an endpoint in clinical trials.
Spatial Distribution of Employment in Hermosillo, 1999–2004
Authors: Rodríguez-Gámez Liz , Dallerba Sandy
Published: June 2012

While the suburbanisation process has been well documented in some large cities of several developed countries, much less attention has been devoted to the case of small and middle-sized cities in developing countries. This article focuses on an exploratory spatial data analysis to investigate the location of the central business district (CBD) and other employment centres in Hermosillo, Mexico. The results reveal the significant presence of spatial dependence and spatial heterogeneity, although their extent varies with the sector under study. These spatial effects take the form of a persistent cluster of high values of employment around the historical district of the city shaping a huge CBD, although a sub-centre of high values emerges to the south and to the north-west of the CBD in 2004. Overall, Hermosillo is still characterised by a traditional monocentric model, but the role of its CBD has changed.